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  • pharmacokinetics  (107)
  • oxidation  (96)
  • Springer  (203)
  • American Meteorological Society
  • Institute of Physics
  • 1995-1999  (203)
  • 1990-1994
  • 1940-1944
  • 1999  (84)
  • 1996  (119)
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  • Springer  (203)
  • American Meteorological Society
  • Institute of Physics
  • Wiley-Blackwell  (10)
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  • 1995-1999  (203)
  • 1990-1994
  • 1940-1944
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  • 1
    Electronic Resource
    Electronic Resource
    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007045922532
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  • 2
    Electronic Resource
    Electronic Resource
    Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics (1999)
    Springer
    Risk analysis 19 (1999), S. 547-558 
    Details
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007017116171
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  • 3
    Electronic Resource
    Electronic Resource
    Factors affecting bioleaching kinetics of sulfide ores using acidophilic micro-organisms (1999)
    Springer
    BioMetals 12 (1999), S. 1-10 
    Details
    ISSN: 1572-8773
    Keywords: acidophilic ; strain ; oxidation ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Recovery of metal values from sulfide ores by use of acidophilic microorganisms is gaining importance. A number of commercial/pilot plants are setup to find out the techno-economic feasibility of the overall process. The main drawback in the process is the slow kinetics of dissolution of metal values from the sulfide ores. To make the technology e attractive the kinetics should be improved considerably. There are various factors which determine the overall kinetics such as bacterial activity and concentration, iron and sulfur oxidation, oxygen consumption, reactor design and nature of ore. A brief review has been made dealing with the above parameters
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009228210654
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  • 4
    Electronic Resource
    Electronic Resource
    Selective oxidation of secondary amines over titanium silicalite molecular sieves, TS-1 and TS-2 (1996)
    Springer
    Catalysis letters 37 (1996), S. 213-216 
    Details
    ISSN: 1572-879X
    Keywords: titanium silicalites ; oxidation ; amines ; hydrogen peroxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Titanium silicalite molecular sieves, TS-1 and TS-2 having MFI and MEL structures, respectively, catalyze the oxidation of secondary amines to the corresponding hydroxylamines using hydrogen peroxide as the oxidant. Higher concentrations of H2O2 lead to further oxidation of hydroxylamine to nitrone. Diffuse reflectance spectroscopy shows the formation of a titanium peroxo complex upon addition of hydrogen peroxide to the TS-1 catalyst. The titanium peroxo complex oxidizes the substrate and reforms to a titanyl group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807756
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  • 5
    Electronic Resource
    Electronic Resource
    Catalytic oxidation of cyclohexene with molecular oxygen by polyoxometalate-intercalated hydrotalcites (1996)
    Springer
    Catalysis letters 40 (1996), S. 43-45 
    Details
    ISSN: 1572-879X
    Keywords: oxidation ; cyclohexene ; polyoxometalate-intercalated hydrotalcite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Cyclohexene was oxidized with molecular oxygen over transition-metal-substituted polyoxometalate-intercalated hydrotalcites to produce 2-cyclohexene-1-one and 2-cyclohexene-1-ol with high selectivity under mild reaction conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807455
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  • 6
    Electronic Resource
    Electronic Resource
    A broad spectrum catalytic system for removal of toxic organics from water by deep oxidation using dioxygen as the oxidant (1996)
    Springer
    Catalysis letters 40 (1996), S. 95-99 
    Details
    ISSN: 1572-879X
    Keywords: palladium metal ; oxidation ; toxic organics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In water, metallic palladium was found to catalyze the deep oxidation of a wide variety of functional organics by dioxygen at 80–90°C in the presence of carbon monoxide. Several classes of organic compounds were examined: benzene, phenol and substituted phenols, aliphatic and aromatic halogenated compounds, organophosphorus, and organosulfur compounds. In every case, deep oxidation to carbon monoxide, carbon dioxide, and water occurred in high yields, resulting in up to several hundred turnovers over a 24 h period. Since the heterogeneous catalyst can be removed by simple filtration, simultaneous water purification and contaminant destruction becomes feasible. For those substrates that are insoluble in pure water, a mixture of water and perfluorobutyric acid was successfully employed as the solvent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807463
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  • 7
    Electronic Resource
    Electronic Resource
    Alkene selectivity enhancement in the oxidation of propane on calcium-based catalysts (1999)
    Springer
    Catalysis letters 59 (1999), S. 67-72 
    Details
    ISSN: 1572-879X
    Keywords: propane ; oxidation ; calcium-based catalysts ; tetrachloromethane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The oxidation of propane has been investigated in the presence and absence of tetrachloromethane (TCM) on calcium hydroxyapatite (CaHAp), Ca3(PO4)2, CaSO4 and CaO at 723 K. In the absence of TCM, the conversion of C3H8 on CaHAp was 7.7–9.2% during 6 h on-stream while that on Ca3(PO4)2, CaSO4 and CaO was 0.6, 0 and 0.2–0.4%, respectively. The principal products on all catalysts in the absence of TCM were CO and CO2 with small selectivities to C3H6 and C2H4 (both 5–6%) observed on CaHAp. Upon addition of TCM, the selectivity to C3H6 on all catalysts and the conversion of C3H8 on CaSO4 increased while, with increasing time-on-stream, the changes in the conversion and selectivity were dependent upon the nature of the catalysts. XPS and XRD analyses provide evidence for the presence of chlorine in the surface and/or bulk of three of the catalysts, suggesting that chlorinated species on the solids play a role in the selectivity enhancement, but the absence of chlorine from the sulphate demonstrates the dissimilarities of the catalysts in their abilities to sorb and decompose TCM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019091731368
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  • 8
    Electronic Resource
    Electronic Resource
    Synergistic effects in the oxidation of methane on strontium and lead hydroxyapatites (1999)
    Springer
    Catalysis letters 57 (1999), S. 161-165 
    Details
    ISSN: 1572-879X
    Keywords: methane ; oxidation ; strontium hydroxyapatite ; lead hydroxyapatite ; tetrachloromethane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The oxidation of methane has been investigated on lead hydroxyapatite (PbHAp), strontium hydroxyapatite (SrHAp) and their binary mixtures at 873 K. PbHAp showed no activity for the oxidation of methane, while SrHAp produced carbon monoxide selectively at 2–4% conversion. On binary mixtures of the hydroxyapatites the conversion of methane and the selectivity to C2 compounds reached values higher than those of the separate constituents of the mixture. With tetrachloromethane in the feed stream a similar synergistic effect was observed with conversions of methane and selectivities to CH3Cl higher on the binary mixtures than those on either SrHAp or PbHAp. The strontium-containing hydroxyapatite appears to play a crucial role in the activation of methane, while the presence of the lead-containing analogue is apparently required for the minimization of undesirable processes involving methyl radicals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019024421857
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  • 9
    Electronic Resource
    Electronic Resource
    A new process for acetic acid production by direct oxidation of ethylene (1999)
    Springer
    Catalysis surveys from Japan 3 (1999), S. 55-60 
    Details
    ISSN: 1572-8803
    Keywords: acetic acid ; oxidation ; Pd ; heteropoly acid ; ethylene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new process for acetic acid production by direct oxidation of ethylene which was established and commercialized is described. The catalyst system consisting of Pd and heteropoly acid exhibits excellent activity and selectivity. The addition of Se or Te to the catalyst system is effective to suppress the formation of carbon dioxide. This new process is applicable to a plant of a wide range of size corresponding to the local demand. Because this new process produces little waste water, it is very friendly to the environment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019003230537
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  • 10
    Electronic Resource
    Electronic Resource
    Oxidative dehydrogenation of ethane over La1−xSrxFeO3−δ perovskite oxides (1996)
    Springer
    Catalysis letters 38 (1996), S. 189-195 
    Details
    ISSN: 1572-879X
    Keywords: perovskite ; La1−xSrxFeO3−δ ; dehydrogenation ; oxidation ; ethane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Catalysts of the composition La1−xSrxFeO3−δ, 0⩽x ⩽1, have been tested for the oxidative dehydrogenation of ethane in the temperature range 300–800°C. The catalyst is active above 400°C, giving a maximum yield of 37% ethylene at 650°C. Above 650°C, synthesis gas was formed together with methane, suggesting that the reforming reaction and thermal cracking of ethane took place. The catalytic data are compared to conductivity measurements on the same material, and a good correlation between the activity and p-type conductivity has been found. In the phase diagram for the system LaFeO3-SrFeO3−δ, a phase separation to two types of (La, Sr)FeO3−δ perovskites was observed in the La/Sr binary composition in the temperature range below 800°C. The phase separation can elucidate the dependency of the catalytic activity on its p-type conductivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00806567
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  • 11
    Electronic Resource
    Electronic Resource
    Inhibition of CO oxidation on hydroxyapatite by tetrachloromethane (1996)
    Springer
    Catalysis letters 39 (1996), S. 205-208 
    Details
    ISSN: 1572-879X
    Keywords: oxidation ; hydroxyapatite ; carbon monoxide ; inhibition ; tetrachloromethane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The introduction of tetrachloromethane (TCM) into the feedstream of CO and O2 inhibits the formation of CO2 on hydroxyapatite. TCM interacts with the surface of hydroxyapatite to form its chlorinated analogue, chlorapatite, which suppresses the oxidation of CO to CO2. Thus, in the oxidative coupling of methane the beneficial effects of the addition of TCM to the feedstream result, at least in part, from the suppression of the further oxidation of CO.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00805584
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  • 12
    Electronic Resource
    Electronic Resource
    A study of “superacidic” MoO3/ZrO2 catalysts for methane oxidation (1999)
    Springer
    Catalysis letters 57 (1999), S. 109-113 
    Details
    ISSN: 1572-879X
    Keywords: superacid ; zirconia ; molybdenum oxide ; methane ; oxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A series of zirconia-supported molybdenum oxide catalysts with different molybdenum loadings prepared using conditions reported to generate “superacidity” have been evaluated for their performance as catalysts for methane oxidation. A marked dependence of Mo content on activity has been observed, with the most active material being that with intermediate molybdenum content. 5 wt% MoO3/ZrO2 compares favourably with ZrxCe1-xO2 for methane combustion. The presence of MoO3 is observed to stabilise the tetragonal polymorph of ZrO2 and, as Mo content is increased, dispersed MoO3 crystallites are formed as evidenced by Raman spectroscopy. Temperature-programmed reduction studies evidence differences in the reduction behaviour of the materials as a function of loading. The results indicate that molybdenum oxide supported on monoclinic zirconia gives rise to the most active catalyst. It is tentatively suggested that the formation of a MoO3 monolayer during reaction may be of importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019047632335
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  • 13
    Electronic Resource
    Electronic Resource
    Oxidation of methanol at copper surfaces (1996)
    Springer
    Catalysis letters 37 (1996), S. 79-87 
    Details
    ISSN: 1572-879X
    Keywords: methanol ; oxidation ; copper ; electron spectroscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The role of preadsorbed oxygen present at Cu(111), Cu(110) and polycrystalline surfaces in the oxidation of methanol has been investigated by X-ray and electron energy loss spectroscopies. In addition to the well established formation of methoxy species and its subsequent decomposition and desorption as formaldehyde, a second reaction pathway to surface formate is present. The latter is temperature dependent being undetectable at 260 K at a polycrystalline surface but occurs at a significant rate at 295 K and above. The limitations of experimental data for methanol oxidation by temperature programmed desorption and molecular beam techniques are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00813523
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  • 14
    Electronic Resource
    Electronic Resource
    Synergistic effects during CO oxidation over mixed oxides. Study of (Fe2O3+SnO2) and (Mn2O3+SnO2) systems (1996)
    Springer
    Catalysis letters 37 (1996), S. 181-185 
    Details
    ISSN: 1572-879X
    Keywords: synergistic effect ; carbon monoxide ; oxidation ; mixed oxides ; iron oxide ; tin oxide ; manganese oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Based on the comparative evaluation of the catalytic activity of Fe2O3, Mn2O3 and SnO2 and their mixed oxides (Fe2O3+SnO2) and (Mn2O3+SnO2), it is shown that the system (Mn2O3+SnO2) shows strong synergistic effects during CO oxidation reaction. Such effects are not observed for the analogous system (Fe2O3+SnO2). Based on the calcination and reduction behaviour of these two mixed oxide systems and the redox potentials of the involved cations, the possible reasons for the observance of synergistic effects for the (Mn2O3+SnO2) system are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807751
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  • 15
    Electronic Resource
    Electronic Resource
    Non-uniform surface kinetics with two types of sites: the case of ethanol oxidation on molybdenum oxide (1996)
    Springer
    Catalysis letters 39 (1996), S. 67-71 
    Details
    ISSN: 1572-879X
    Keywords: non-uniform surface ; kinetics ; ethanol ; oxidation ; molybdenum oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Temkin's theory of rates of catalytic reactions on non-uniform surfaces is extended to the MoO3-catalyzed oxidation of ethanol to acetaldehyde. Two types of sites are assumed to be present, an oxygen atom site that can be modeled with uniform properties and a metal atom site characterized by non-uniform properties both for ethanol chemisorption to an ethoxide intermediate and the conversion of this intermediate to acetaldehyde. The rate-limiting step is the cleavage of a C-H bond in the absorbed ethoxide intermediate. Non-uniform surface kinetics leads to a kinetic rate expression of the form $$v = kP_{C_2 H_5 OH}^{1 - m} P_{O_2 }^{(1 - m)/4} P_{H_2 O}^{ - (1 - m)/2} $$ . Such a rate expression, withm=0.14, is shown to provide a good fit to kinetic data for the selective oxidation of ethanol on a silica supported molybdenum oxide catalyst.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00813732
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  • 16
    Electronic Resource
    Electronic Resource
    Baeyer-Villiger rearrangement catalysed by titanium silicate molecular sieve (TS-1)/H2O2 system (1996)
    Springer
    Catalysis letters 40 (1996), S. 47-50 
    Details
    ISSN: 1572-879X
    Keywords: Baeyer-Villiger ; titanium silicate molecular sieve ; oxidation ; rearrangement ; titanium peroxo ; triphase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Titanium silicate molecular sieve TS-1 has been found to be an efficient catalyst for Baeyer-Villiger (BV) oxidation of cyclic and aromatic ketones under triphase conditions (solid catalyst along with two immiscible liquid reactants in the absence of any cosolvent), using dilute H2O2. Reactions studied are the oxidation of cyclohexanone and acetophenone. Whereas in the case of cyclohexane,ε-caprolactone, a BV product along with hydroxy and diketones is formed, in the case of acetophenone, phenyl acetate, a BV product along witho- andp-hydroxyacetophenone is formed. The acidic nature of titanium peroxo species, stabilised by water, is proposed to be responsible for such reactions under triphasic reaction conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807456
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  • 17
    Electronic Resource
    Electronic Resource
    Platinum particle size effect on the oxidative dehydrogenation of aqueous ethanol (1996)
    Springer
    Catalysis letters 36 (1996), S. 31-36 
    Details
    ISSN: 1572-879X
    Keywords: ethanol ; kinetics ; oxidation ; oxydehydrogenation ; platinum ; structure sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of the platinum particle size was investigated for the catalytic oxidative dehydrogenation of aqueous ethanol to ethanal at a temperature of 303 K, an ethanol concentration of 260 mol m−3, a partial oxygen pressure 60 kPa, a pH of 9, and an ethanal and ethanoate concentration of 20 mol m−3. A particle size effect on the turnover frequency was observed but only for particle sizes smaller than 2 nm. Hence, the reaction shows a limited structure sensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807202
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  • 18
    Electronic Resource
    Electronic Resource
    Perfluoroalkylporphyrin complexes as active catalysts for the reaction of isobutane with oxygen and the decomposition of tert-butyl hydroperoxide (1996)
    Springer
    Catalysis letters 36 (1996), S. 69-73 
    Details
    ISSN: 1572-879X
    Keywords: oxidation ; metalloporphyrins ; hydroperoxide decomposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new family of metalloporphyrin complexes having perfluoroalkyl groups in the meso-positions of the ring are active catalysts for the oxidation of isobutane to tert-butyl alcohol, TBA, and for the decomposition of tert-butyl hydroperoxide to TBA. This discovery extends the limited number of meso-substituents that can be used to enhance catalytic activity and fits the postulate that groups that withdraw electrons from the porphyrin periphery give rise to active catalysts for alkane oxidation. The perfluoroalkyl groups also confer oxidative stability, hydrophobicity and lower cost to the catalyst.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807207
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  • 19
    Electronic Resource
    Electronic Resource
    A new strategy for alkane oxidation with O2 using N‐hydroxyphthalimide (NHPI) as a radical catalyst (1999)
    Springer
    Catalysis surveys from Japan 3 (1999), S. 27-35 
    Details
    ISSN: 1572-8803
    Keywords: oxidation ; oxygen ; alkane ; N‐hydroxyphthalimide ; radical catalyst
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A practical catalytic method to convert alkanes into the corresponding oxygen‐containing compounds with O2 under mild conditions using N‐hydroxyphthalimide (NHPI) in the presence or absence of a transition metal was developed. Thus, cyclohexane was successfully converted into adipic acid in good conversion and selectivity by a combined catalytic system consisting of NHPI and Mn(acac)2. Lower alkane such as isobutane was converted into t‐butyl alcohol (83%) under 10 atm of air by NHPI‐Co(OAc)2 system. Alkylbenzene such as toluene was oxidized to benzoic acid in high yield (81%) under normal temperature and pressure of dioxygen in the presence of a catalytic amount of NHPI and Co(OAc)2. ESR measurements showed that phthalimide‐N‐oxyl generated from NHPI under dioxygen atmosphere is a key species in this oxidation and functions as a radical catalyst.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019059315516
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  • 20
    Electronic Resource
    Electronic Resource
    Electrochemical oxidation of a carbon black loaded polymer electrode in aqueous electrolytes (1999)
    Springer
    Journal of solid state electrochemistry 3 (1999), S. 179-186 
    Details
    ISSN: 1433-0768
    Keywords: Key words Cathodic protection system ; Carbon ; oxidation ; Composite carbon/polymer anode ; Lifetime
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The suitability of a polymeric composite material for use as part of an anode structure in a cathodic protection system has been examined. The composite material was a conductive blend (volume resistivity typically 1.5 Ω cm) of carbon black in a polyethylene binder. A long operational lifetime for the material demands that the rate of carbon loss must be low. In the work reported here, electrochemical and in situ analytical techniques were employed to characterise the performance of the material over a wide range of anodic current densities in a variety of aqueous electrolytes. The predominant anodic electrochemical reaction on the polymeric material is CO2 formation in acid and neutral solutions, which causes loss of carbon from the surface and the development of a non-conducting layer of polyethylene. The characteristics of the reaction suggest that it occurs via the discharge of H2O. In alkaline pH, however, the anodic reactions are more complex. A high OH− concentration (pH 12 or higher) favours the formation of oxygen rather than CO2, particularly at low anodic potentials. The presence of CO3 2− in the electrolyte catalyses the evolution of oxygen at pH values as low as 9. The electrochemical formation of oxygen always occurs in parallel with the generation of some humic acid in the solution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100080050145
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  • 21
    Electronic Resource
    Electronic Resource
    Influence of age, frailty and liver function on the pharmacokinetics of brofaromine (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 387-391 
    Details
    ISSN: 1432-1041
    Keywords: Key words Liver function tests; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h⋅l−1, clearance was reduced (5.0 vs. 11.8 l⋅h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P 〈 0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050037
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    Design of a suitable formulation of FK613, a novel antiallergic agent, based on its pharmacokinetic and pharmacodynamic properties in healthy subjects (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 279-284 
    Details
    ISSN: 1432-1041
    Keywords: Antiallergic drug ; FK613 ; pharmacokinetics ; histamine skin-test ; drug formulation ; urinary excretion ; safety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and 〉89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80–250 ng · ml-1 was recommended to ensure the suppression of histamine-induced wheal by 〉50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00226328
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    Multiple dose pharmacokinetics of tiludronate in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 175-181 
    Details
    ISSN: 1432-1041
    Keywords: Key words Tiludronate; healthy volunteers ; bisphosphonates ; pharmacokinetics ; calcium metabolism ; bone resorption ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: A double-blind, placebo-controlled study was conducted to assess the pharmacokinetics and pharmacodynamics of the bisphosphonate tiludronic acid, administered once daily as sodium tiludronate 200, 400, 600 and 800 mg for 12 days. Four groups of ten subjects participated in the study, with a drug to placebo ratio of 4:1. Methods: Pre-dose blood samples were taken on alternate days, starting on Day 1 and additional samples were collected over 144 h following the final dose on Day 12. Urine was collected over 24 h after the final dose. Indices of calcium homeostasis and biochemical markers of bone turnover were assessed during the study as pharmacodynamic parameters. Tolerability was evaluated with special emphasis on renal function and gastrointestinal irritation. Adverse experiences were assessed at regular time intervals. Results and conclusions: Steady state was attained from Day 4 (200 mg) or from Day 6 (400, 600 and 800 mg). Following the final dose on Day 12, minimal plasma concentrations (Cmin) ranged between 0.19 and 1.5 mg ⋅ l−1, and maximal plasma concentrations (Cmax) between 1.1 and 7.8 mg⋅l−1 for the lowest and highest doses, respectively. A supra-proportional increase in Cmax, AUC24 and Ae 24 with dose was observed. There was a linear relationship between the plasma tiludronic acid and its urinary excretion rate, so, the disproportional rise in Cmax and AUC24 with increasing dose could not be attributed to saturation of renal excretion. Certain indices of calcium homeostasis changed significantly during the study, but generally, became only prominent at the highest dose level of 800 mg. Total serum calcium and the urinary calcium/creatinine clearance ratio fell, indicating depression of osteoclastic bone resorption, which was not revealed by serum osteocalcin levels probably because of the brevity of the treatment (12 days). In response to the decline in serum calcium, serum 1,25-dihydroxyvitamin D3 and intact PTH (1–84) levels increased. None of the safety parameters raised any concerns about the safety of sodium tiludronate administered in this way.
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    URL: http://dx.doi.org/10.1007/s002280050181
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    Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 189-193 
    Details
    ISSN: 1432-1041
    Keywords: Key words Dihydropyridine ; Amlodipine ; Grapefruit juice; flavonoids ; interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: This study was performed to assess whether coadminstration with grapefruit juice significantly affects the pharmacokinetics of amlodipine, a dihydropyridine class calcium antagonist with slow absorption, distribution and low plasma clearance. The primary objective was to evaluate whether short exposure to grapefruit juice could affect the metabolism of amlodipine to an extent similar to that previously demonstrated for other dihydropyridines (e.g. felodipine, nisoldipine, nitrendipine). Methods: Twelve healthy male volunteers followed a randomised, open crossover study design, comparing the effect of a single oral dose of amlodipine (5 mg) taken together with a glass of grapefruit juice (250 ml) vs water. Blood samples to determine plasma concentration were taken and blood pressure (BP) and heart rate (HR) were measured throughout the study. Results: When amlodipine was coadministered with grapefruit juice, Cmax was 115% and AUC(0–72 h) was 116% compared with water, but tmax was not significantly changed. There were no significant differences in BP and HR between the two treatments. A small decrease in diastolic BP, however, was observed in both treatments 4–8 h after drug administration, coinciding with Cmax, but this was normalised after 12 h. The BP reduction seen was compensated by a slight increase in HR, which remained throughout the study. Conclusion: An interaction between grapefruit juice and amlodipine was demonstrated. The haemodynamic data showed that a dose of 5 mg was sufficient to achieve a BP reduction in healthy subjects, but the increase in amlodipine plasma concentration seen after intake of grapefruit juice was too small to significantly affect BP or HR. The clinical significance of this food/drug interaction, however, cannot be ignored since there is considerable variation between individuals and a more extensive intake of grapefruit juice might give more pronounced effects.
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    URL: http://dx.doi.org/10.1007/s002280050183
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    Haemodynamic effects and pharmacokinetics of oral d-and l-nebivolol in hypertensive patients (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 259-264 
    Details
    ISSN: 1432-1041
    Keywords: Key words Nebivolol ; Hypertension; d ; l-enantiomers ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Nebivolol is a selective β1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. Methods: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. Results: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml ⋅ 100 ml−1 tissue) as compared to active nebivolol treatment (5.17 ml ⋅ 100 ml−1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml ⋅ 100 ml−1 tissue) or on active treatment (5.97 ml ⋅ 100 ml−1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). Conclusions: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.
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    URL: http://dx.doi.org/10.1007/s002280050194
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    Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 277-281 
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    ISSN: 1432-1041
    Keywords: Key words Pantoprazole; Proton pump inhibitor drug interaction ; oral anticoagulant phenprocoumon ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC0–24h and Cmax of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0–24h and of Cmax of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC0–24h; 0.95, 0.88–1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
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    URL: http://dx.doi.org/10.1007/s002280050198
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    Influence of age, frailty and liver function on the pharmacokinetics of brofaromine (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 387-391 
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    ISSN: 1432-1041
    Keywords: Liver function tests ; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h·l−1, clearance was reduced (5.0 vs. 11.8 l·h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r=0.41, P=0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r=0.94, P〈0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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    URL: http://dx.doi.org/10.1007/BF00203783
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    Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 411-415 
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    ISSN: 1432-1041
    Keywords: Moxisylyte ; pharmacokinetics ; intracavernous administration ; healthy volunteers ; adverse events ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The concentration-time profiles of specific metabolites of moxisylyte, an α-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg). Results: Four metabolites, unconjugated desacetyl-moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulphates were found in plasma and urine. For all metabolites, t1/2 elimination was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and AUC increased in direct proportion to dose, except for the inactive DAM glucuronide. Any the differences detected were small and equivalence of the three doses can be accepted. Conclusion: The pharmacokinetics of moxisylyte in humans following intracavernous administration were linear in the dose range 10 to 30 mg.
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    URL: http://dx.doi.org/10.1007/BF00203788
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    Rectal pharmacokinetics of budesonide (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 293-298 
    Details
    ISSN: 1432-1041
    Keywords: Key words Budesonide; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol ⋅ l−1 (0.95–8.2), 3.0 nmol ⋅ l−1 (0.64–8.9) and 1.3 nmol ⋅ l−1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax = 1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax = 2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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    URL: http://dx.doi.org/10.1007/BF00226330
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    Electronic Resource
    Electronic Resource
    Rectal pharmacokinetics of budesonide (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 293-298 
    Details
    ISSN: 1432-1041
    Keywords: Budesonide ; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol·l-1 (0.95–8.2), 3.0 nmol·l-1 (0.64–8.9) and 1.3 nmol·l-1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax=1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax=2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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    Increase in magnesium plasma level after orally administered trimagnesium dicitrate (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 317-323 
    Details
    ISSN: 1432-1041
    Keywords: Magnesium ; Plasma level ; pharmacokinetics ; bioavailability ; circadian fluctuation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.
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    URL: http://dx.doi.org/10.1007/BF00226334
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    Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 47-55 
    Details
    ISSN: 1432-1041
    Keywords: Key words Tolcapone ; Elderly; levodopa ; pharmacokinetics ; pharmacodynamics ; multiple-dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. Methods: The drug was administered orally t.i.d. for 7 days to four sequential groups of eight elderly subjects (gender ratio1:1) at doses of 100, 200, 400 and 800 mg in a double-blind, randomised, placebo-controlled, ascending-multiple-dose design. On days 2 and 7, a single dose of levodopa/benserazide 100/25 mg was given 1 h after the first intake of tolcapone. Plasma concentrations of tolcapone, its metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa were determined during the course of the study in conjunction with COMT activity in erythrocytes. Results: Tolcapone was well tolerated at all dose levels, with a slight increase in gastrointestinal adverse events in females at higher doses. The drug was rapidly absorbed and eliminated and showed no changes in pharmacokinetics with time during multiple doses of 100 and 200 mg t.i.d. At doses of 400 and 800 mg t.i.d., tolcapone accumulated moderately as reflected in increased Cmax and AUC values. Despite the long half-life of 3-O-methyltolcapone (39 h), only minor accumulation occurred due to suppression of its formation by tolcapone. The pharmacodynamics of tolcapone did not change during the week of treatment as reflected in inhibition of COMT activity in erythrocytes, the derived parameters of the plasma concentration-effect relationship (inhibitory Emax model with constant EC50 values) and the effect on levodopa pharmacokinetics (1.6 to 2.5-fold increase in bioavailability). This suggests the absence of tolerance development and the insignificance of the altered pharmacokinetics at 400 and 800 mg t.i.d. with regard to the pharmacodynamics. Conclusion: The results of this study offer promising perspectives for the application of tolcapone as adjunct therapy to levodopa in the treatment of Parkinson’s disease.
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    URL: http://dx.doi.org/10.1007/s002280050068
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    A comparison of the pharmacokinetics and pharmacodynamics of cilazapril between Chinese and Caucasian healthy, normotensive volunteers (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 57-62 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cilazapril ; Caucasians ; Chinese; cilazaprilat ; pharmacokinetics ; pharmacodynamics ; ACE inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Methods: The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 12 Chinese and 13 Caucasian, healthy, normotensive volunteers on their normal diet. Cilazapril was given orally as a single 2.5 mg capsule. Plasma was sampled for assay of the active metabolite, cilazaprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE-activity. Plasma concentrations of the active drug were measured by radioimmunoassay. Blood pressure and heart rate were measured at regular intervals. Results: The pharmacokinetic parameters of cilazaprilat were similar in the two ethnic groups. No significant difference in plasma concentrations was found at any of the time points. However, the weight-adjusted plasma clearance was significantly higher in the Chinese group, which is compatible with their lower body weight. The effects on plasma hormones were also comparable, although there was a somewhat greater rise in PRA and greater fall in aldosterone levels in Chinese than in Caucasians. The effect of cilazapril on blood pressure and heart rate was greater than was previously reported in healthy volunteers. Systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced in both groups, but there was a more prolonged reduction in DBP in Caucasians. In addition, heart rate (HR) was significantly increased from baseline from 5 h onwards in Chinese subjects and significantly higher in comparison with Caucasians at most time points from 1.5 h onwards. The pharmacokinetic parameters of cilazapril were essentially the same in healthy, normotensive Chinese and Caucasians. Cilazapril reduced blood pressure acutely in both groups, with good tolerance. The inhibition of ACE in relationship to time and the plasma concentrations of cilazaprilat were similar in the two groups, although the changes in PRA and aldosterone suggest an ethnic difference in the responses of the renin-angiotensin-aldosterone system.
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    URL: http://dx.doi.org/10.1007/s002280050069
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    Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 203-208 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cyclosporine ; Felodipine; dehydrofelodi-pine ; pharmacokinetics ; blood pressure ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine, and 24-hour blood pressure measurements. Methods: Single doses of cyclosporine (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets 10 mg) were given at a 1–2 week interval. Plasma drug concentrations were followed for 2 days after drug intake. Results: For cyclosporine, Cmax was increased after combined treatment (16%) compared to cyclosporine alone, but felodipine did not influence other kinetic parameters of cyclosporine. For felodipine, combined treatment with cyclosporine and felodipine increased AUC and Cmax (58% and 151%, respectively) and lowered mean residence time (24%) significantly compared to felodipine alone. For the metabolite dehydrofelodipine, too, AUC and Cmax were increased after the combined treatment (43% and 94%, respectively). Mean 24-hour systolic and diastolic blood pressures were significantly lower after felodipine, both when felodipine was given alone (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to cyclosporine alone (127/73 mmHg). Conclusion: A combined single dose of cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of felodipine suggesting a cyclosporine-induced decrease in the first-pass metabolism of felodipine, whereas the AUC of cyclosporine was only slightly increased by felodipine.
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    URL: http://dx.doi.org/10.1007/s002280050093
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    Effect of food on the bioavailability of oxybutynin from a controlled release tablet (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 221-223 
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    ISSN: 1432-1041
    Keywords: Key words Oxybutynin; effect of food ; N-desethyl oxybutynin ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. Results: Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20% . The Cmax of oxybutynin and N-desethyl oxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. Conclusion: Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.
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    URL: http://dx.doi.org/10.1007/s002280050096
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    Plasma concentrations and pharmacokinetics of idebenone and its metabolites following single and repeated doses in young patients with mitochondrial encephalomyopathy (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 167-169 
    Details
    ISSN: 1432-1041
    Keywords: Key words Idebenone; mitochondrial encephalomyopathy ; young patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics and tolerance of idebenone after single or repeated doses have been studied in young patients with mitochondrial encephalomyopathy. Results: No significant adverse effects were noted. In 3 out of 7 patients idebenone induced overall stimulation and improvement in arousal. Plasma concentrations of idebenone and its main metabolites were determined and the pharmacokinetic parameters of idebenone after single and repeated doses were estimated. During the single dose study, the mean plasma concentrations of idebenone and its main metabolites and mean pharmacokinetic parameters were comparable to published results (Cmax = 452.2 ng ⋅ ml−1, tmax = 2.3 h, AUC = 26 μg ⋅ ml−1 ⋅ h, t1/2β = 16.5 h). During the repeated doses study, no significant difference was found between mean residual plasma concentrations of idebenone on Day 2 (47 ng ⋅ ml−1) and Day 5 (70.6 ng ⋅ ml−1), and mean t1/2β of idebenone after the single and after repeated dose studies, i.e., there was no evidence of accumulation. Although idebenone did not appear to accumulate during this study, the coadministration of anticonvulsants, often prescribed during mitochondrial encephalomyopathy, can affect its pharmacokinetics.
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    Single oral doses of amisulpride do not enhance the effects of alcohol on the performance and memory of healthy subjects (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 161-166 
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    ISSN: 1432-1041
    Keywords: Key words Amisulpride; ethanol vector ; performance ; memory ; cognitive function ; interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D2- and D3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible interaction with alcohol on human performance, amisulpride was studied for this potential. Methods: In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride 50 mg and 200 mg, without and with ethanol (0.8 g ⋅kg−1) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions were confirmed by factorial contrast ANOVA. Results: Mean blood ethanol was 0.94, 0.62 and 0.26 g ⋅l−1 at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations of amisulpride were little changed by ethanol. Conclusions: Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically.
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    Comparison between concentrations of racemic mefloquine, its separate enantiomers and the carboxylic acid metabolite in whole blood serum and plasma (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 171-173 
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    ISSN: 1432-1041
    Keywords: Key words Mefloquine; mefloquine enantiomers ; carboxylic acid metabolite ; blood concentrations ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To compare concentrations of the separate enantiomers of mefloquine (MQ), total racemic MQ and the carboxylic acid metabolite in different blood fractions at steady state. Setting: Human volunteer laboratory, Unit of Clinical Pharmacology, Karolinska Institute. Volunteers: Ten healthy adult Caucasian volunteers. Methods: Drug concentrations were determined by high-performance liquid chromatography (HPLC). Results: Trough concentrations of the (+)RS enantiomer were higher in venous whole blood than in plasma and serum (mean ratios, 1.41 and 1.38). For the other enantiomer, (−)SR, concentrations were lower in whole blood than in plasma (mean ratio 0.89) and for the metabolite this ratio was 0.5. Conclusion: Stereoselective distribution might be important for antimalarial activity and should be considered when pharmacokinetic studies are performed.
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    Pharmacokinetics of dexamethasone in premature neonates (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 477-483 
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    ISSN: 1432-1041
    Keywords: Dexamethasone ; Premature neonates ; pharmacokinetics ; bronchopulmonary dysplasia ; infant ; newborn
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Dexamethasone is frequently used in premature neonates with bronchopulmonary dysplasia, however little is known about its disposition in this population. Methods: We evaluated the pharmacokinetics of dexamethasone in 9 premature neonates with a mean gestational age of 27.3 weeks and a postnatal age of 21.8 days. Results: There was a strong relationship between clearance (4.96 ml·min−1·kg−1) and gestational age (r=0.884). Pharmacokinetic parameters were grouped based on a gestational age of less than 27 weeks (Group I) and greater than 27 weeks (Group II). Mean clearance in group I and group II was 1.69 and 7.57 ml·min−1·kg−1, respectively. Mean distribution volume in group I and II was 1.26 and 2.19 l·kg−1, respectively. No significant relationships were noted between the disposition of dexamethasone and ventilator requirements or adverse effects. Conclusion: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.
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    Influence of food on the bioavailability and some pharmacokinetic parameters of diprafenone – a novel antiarrhythmic agent (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 315-319 
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    ISSN: 1432-1041
    Keywords: Key words Diprafenone; antiarrhythmics ; bioavailability ; human ; foods ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was done to investigate the effect of food on the bioavailability of diprafenone. Methods: The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite were determined up to 24 hours after administration by a sensitive, specific HPLC method. Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only data from the rapid hydroxylators were used in the statistical analysis. Results: Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow hydroxylators. The only slow hydroxylator in this trial had an AUC0–last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal relationship to food.
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    Evaluation of plasma and urinary salbutamol levels in COPD (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 91-93 
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    ISSN: 1432-1041
    Keywords: Key words Salbutamol; nebulised ; pharmacokinetics ; COPD ; overnight urinary salbutamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To evaluate the use of trough plasma salbutamol and overnight urinary salbutamol excretion in the assessment of nebulised salbutamol delivery in patients with chronic obstructive pulmonary disease (COPD). Methods: Twenty in-patients with COPD receiving nebulised salbutamol, age 69.7 years, FEV1 38.1% predicted, were studied on two consecutive days, receiving four 2.5 mg doses of nebulised salbutamol on day 1 and four 5 mg doses of nebulised salbutamol on day 2, the first dose at 8.00 h the last dose at 22.00 h. Salbutamol delivery was assessed after the last dose by trough plasma salbutamol 8.00 h and overnight urinary excretion of salbutamol (22.00–8.00 h). Results: Levels of urinary salbutamol were detectable in all 20 patients at both doses, whereas for plasma salbutamol detectable levels were only found in 16/20 cases at the 2.5 mg dose and in all cases at the 5 mg dose. For overnight urinary salbutamol (μg⋅10 h−1  n = 20) the results were 141 for 2.5 mg and 249 for 5 mg. The dose ratio for urinary salbutamol between 2.5 mg and 5 mg doses was 1.83. Results for plasma salbutamol (ng/ml, n = 16) were 1.58 at 2.5 mg and 2.43 at 5 mg: dose ratio (geometric mean) 1.49. Conclusion: Overnight urinary salbutamol provides a simple and effective measure of nebulised salbutamol delivery in patients with COPD, which would be suitable for studying nebuliser performance and compliance.
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    Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 485-489 
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    ISSN: 1432-1041
    Keywords: Key words Nalbuphine ; Neonate; therapeutic drug monitoring ; placental transfer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a systemic analgesic during labour. Recent reports of perinatal adverse effects prompted us to carry out therapeutic nalbuphine monitoring in obstetric analgesia. Because data on fetomaternal transfer are scarce and the pharmacokinetics of this drug in the neonate are largely unknown, we report data obtained from 28 parturients treated with nalbuphine either intramuscularly and/or intravenously during labour. Plasma nalbuphine levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. At delivery, 30–150 min after maternal administration, nalbuphine concentrations ranged from 5.0 to 79.2 ng ⋅ ml−1 in mother plasma samples and from 3.0 to 46.6 ng ⋅ ml−1 in umbilical cord plasma samples. Nalbuphine concentrations were highly correlated to dose. The fetomaternal ratio was high: 0.74 and not correlated to the administered dose of nalbuphine. An estimated plasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuphine concentrations. Apart from a flattening of the fetal heart rate tracing in 54% of the cases, only one neonate had a low Apgar score at birth. The apparent prolonged half-life of nalbuphine in the neonate indicates the usefulness of an intramuscular injection of naloxone to prevent recurrence of cardiorespiratory depression due to nalbuphine administration to the mother.
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    Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 485-489 
    Details
    ISSN: 1432-1041
    Keywords: Nalbuphine ; Neonate ; therapeutic drug monitoring ; placental transfer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a systemic analgesic during labour. Recent reports of perinatal adverse effects prompted us to carry out therapeutic nalbuphine monitoring in obstetric analgesia. Because data on fetomaternal transfer are scarce and the pharmacokinetics of this drug in the neonate are largely unknown, we report data obtained from 28 parturients treated with nalbuphine either intramuscularly and/or intravenously during labour. Plasma nalbuphine levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. At delivery, 30–150 min after maternal administration, nalbuphine concentrations ranged from 5.0 to 79.2 ng·ml−1 in mother plasma samples and from 3.0 to 46.6 ng·ml−1 in umbilical cord plasma samples. Nalbuphine concentrations were highly correlated to dose. The fetomaternal ratio was high: 0.74 and not correlated to the administered dose of nalbuphine. An estimated plasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuphine concentrations. Apart from a flattening of the fetal heart rate tracing in 54% of the cases, only one neonate had a low Apgar score at birth. The apparent prolonged half-life of nalbuphine in the neonate indicates the usefulness of an intramuscular injection of naloxone to prevent recurrence of cardiorespiratory depression due to nalbuphine administration to the mother.
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    Pharmacokinetics of quinine in patients with chronic renal failure (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 497-501 
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    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Methods: We investigated the pharmacokinetics of quinine (Qn) following administration of a single oral dose of 600 mg Qn sulphate in six male Thai patients with a moderate degree of chronic renal failure (CRF), and six male Thai subjects with normal renal function. Results: The drug was well tolerated in both groups of subjects; no major adverse reactions were observed. A marked alteration in the pharmacokinetics of Qn was found in patients with CRF compared to healthy subjects; there were six signifiicant changes in the pharmacokinetic parameters. Absorption was delayed, but increased in CRF (tmax 4.5 vs 1.6 h, Cmax 6.17 vs 3.45 μg·ml−1). Total clearance was significantly reduced 0.94 vs 2.84 ml·min−1·kg−1, whereas Vz/f remained unchanged (1.82 vs 2.78 1·kg−1). This resulted in the increased values of AUC and prolongation of the t1/2z and MRT in the patients (AUC 181.5 vs 61.8 μg·min−1·ml−1, t1/2z 26 vs 9.7 h, MRT 36.4 vs 11.3 h). Median concentrations of plasma unbound fraction of Qn collected at 4 h after drug administration in patients and healthy subjects were 7.3 vs 9.8%, respectively.
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    Stereoselective pharmacokinetics of mefloquine in young children (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 241-244 
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    ISSN: 1432-1041
    Keywords: Key words Mefloquine ; Children; enantiomer ; pharmacokinetics ; stereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: the stereospecificity of mefloquine pharmacokinetics in children has been investigated. Patients: Twelve children aged 6 to 24 months were treated for uncomplicated falciparum malaria with a single oral dose of 25 mg⋅kg−1 racemic mefloquine in combination with sulfadoxine and pyrimethamine. Methods: concentrations of mefloquine enantiomers were determined using a coupled achiral-chiral chromatographic system. Pharmacokinetic parameters were calculated using model-independent analysis. Results: Maximum plasma concentrations, areas under the curve and apparent plasma elimination half-lives were higher for the (−) enantiomer than its antipode. In contrast, the apparent volume of distribution (V/f) and total clearance (Cl/f) values were higher for the (+) enantiomer. Conclusion: the stereoselectivity of mefloquine pharmacokinetics is similar to that observed in adults.
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    A single dose of ursodiol does not affect cyclosporine absorption in liver transplant patients (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 335-337 
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    ISSN: 1432-1041
    Keywords: Key words Cyclosporine ; Ursodiol; ursodeoxycholic acid ; absorption ; pharmacokinetics ; liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To study the possible influence of ursodiol (ursodeoxycholic acid), a hydrophilic bile acid, on cyclosporine (CsA) bioavailability. Methods: Seven adult liver transplant recipients participated in a randomised cross-over pharmacokinetic study comparing ursodiol (600 mg) with placebo in single doses. Blood concentrations of CsA were measured by HPLC. Results: There was no significant effect of ursodiol on CsA absorption: AUC was 5011 vs 5486 ng⋅h⋅ml–1, Cmax was 832 vs 871 ng⋅ml–1 and tmax was 2 vs 2 h, after ursodiol and placebo, respectively. Conclusion: Although a significant period effect was observed, we conclude that a single dose of ursodiol has little effect on CsA absorption in liver transplant patients and that an interaction in the intestinal lumen between these two drugs is unlikely.
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    Absolute bioavailability of fluoride from disodium monofluorophosphate and enteric-coated sodium fluoride tablets (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 321-326 
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    ISSN: 1432-1041
    Keywords: Key words Sodium fluoride ; Disodium monofluorophosphate; absolute bioavailability ; pharmacokinetics ; elderly population
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: The absolute bioavailability and other pharmacokinetic parameters of two fluoride formulations were investigated in 13 healthy volunteers, aged 61–70 years. Methods: The following formulations were administered, under fasting conditions, in a single-dose three-way cross-over design: tablets of 76 mg disodium monofluoro phosphate (MFP, equivalent to 10.0 mg F− ion), enteric-coated (e.c.) tablets of 25 mg sodium fluoride (NaFor, equivalent of 11.3 mg F− ion), and an isoosmotic aqueous injection solution (4 ml) of 22.1 mg sodium fluoride (NaFiv, equivalent of 10.0 mg F− ion). There was a wash-out period of at least one week between each administration. Blood was sampled before and during a 24-hour period after administration. For F− excretion urine was sampled 48 hours before (baseline) and over the 48 hours after the adminstration. Results: The mean t1/2 values of the three formulations were 8.3, 8.7 and 8.3 h for MFP, NaFor and NaFiv respectively, and were not significant different. Mean Cmax after MFP was significantly higher than after NaFor [344 vs 142 μg⋅l−1]. Mean tmax for MFP was shorter than for NaFor [1.1 vs 4.6 h]. MFP had significantly higher bioavailability [102.8%] than NaFor [64.2%]. Conclusion: The MFP formulation showed higher bioavailability with smaller variation than the NaFor formulation. MFP is preferable, therefore, for fluoride therapy in clinical practice, and changing from NaFor to MFP will require adjustment of the dose.
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    Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 491-495 
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    ISSN: 1432-1041
    Keywords: Key words Aprotinin ; Arginine vasopressin; bioavailability ; dDAVP ; enzyme inhibitor ; gastrointestinal tract ; healthy volunteer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration. Methods: For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly, in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml⋅min−1 for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h. Results: The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg−1. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor.
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    Bioavailability of estradiol from a new matrix and a conventional reservoir-type transdermal therapeutic system (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 327-330 
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    ISSN: 1432-1041
    Keywords: Key words Hormone replacement therapy; estradiol ; pharmacokinetics ; bioequivalence ; postmenopausal volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Bioavailability of estradiol delivered from a newly developed matrix-type transdermal therapeutic system (MTTS) was compared with that of the conventional reservoir-type system (RTTS). Both formulations have a nominal delivery rate of 50 μg per day of 17β-estradiol (E2). Plasma concentrations of E2 and estrone (E1) were determined at steady state during a 96-h application of each formulation to 34 postmenopausal volunteers, using a two-stage randomized two-period crossover design. Results: The MTTS proved to be equivalent to the RTTS with respect to the extent of E2 absorption. Due to differences in patch design and composition, the rate of absorption was different between the two systems, with less fluctuating E2 plasma levels during application of the matrix system. Local tolerability and adhesion of MTTS appeared to be better than those of the reservoir system.
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    Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 331-334 
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    ISSN: 1432-1041
    Keywords: Key words Zopiclone ; Itraconazole; drug interaction ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We studied the possible interaction between itraconazole, a potent inhibitor of CYP3A, and zopiclone, a short-acting hypnotic. Methods: A double-blind, randomized, two-phase crossover design was used. Ten healthy young subjects received daily either 200 mg itraconazole or placebo for 4 days. On day 4 they ingested a single 7.5-mg oral dose of zopiclone. Plasma concentrations of zopiclone and itraconazole were determined and pharmacodynamic responses were measured up to 17 h. Results: Itraconazole significantly increased the Cmax of zopiclone from 49 to 63 ng ⋅ ml−1. The t1/2 of zopiclone was prolonged from 5.0 to 7.0 h. The AUC(0–∞) of zopiclone was increased from 415 to 719 ng ⋅ ml−1 h by itraconazole. No statistically significant differences were observed in the pharmacodynamic responses between the groups. Conclusion: Itraconazole has a statistically significant pharmacokinetic interaction with zopiclone but this is only of limited clinical importance, at least in young adults.
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    Effects of heat exposure in a Finnish sauna on the pharmacokinetics and metabolism of midazolam (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 335-338 
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    ISSN: 1432-1041
    Keywords: Key words Midazolam ; Sauna; metabolism ; pharmacokinetics ; heat ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of short-term heat exposure in a Finnish sauna on hepatic first-pass metabolism and the capacity to metabolize midazolam were studied in a crossover trial. Midazolam oral (15 mg) and intravenous (0.05 mg ⋅ kg−1) was given to 6 healthy young male volunteers, in random order, during a control session and a sauna bathing session (temperature 85–100° C, relative humidity 25–30%). Blood samples for the determination of plasma midazolam and α-hydroxy midazolam concentrations were taken for 6 h after drug administration. Results: After oral administration, the bioavailability and clearance of midazolam were not affected by sauna bathing, nor was there a significant difference in α-hydroxy midazolam plasma concentration or the α-hydroxy midazolam/midazolam AUC-ratio between the sessions. Midazolam Cmax was increased and its t1/2β was prolonged during the sauna session, but the clinical relevance of the findings appears to be modest. The pharmacokinetics of intravenous midazolam were not affected by sauna bathing. Conclusions: Short-term heat exposure may not affect the first-pass metabolism or hepatic capacity to metabolize midazolam.
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    Purification and characterization of fumarase from the syntrophic propionate-oxidizing bacterium strain MPOB (1996)
    Springer
    Archives of microbiology 165 (1996), S. 126-131 
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    ISSN: 1432-072X
    Keywords: Key words Fumarase ; Syntrophy ; Propionate ; oxidation ; Fumarate fermentation ; Anaerobic oxidation ; Iron-sulfur cluster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Fumarase from the syntrophic propionate-oxidizing bacterium strain MPOB was purified 130-fold under anoxic conditions. The native enzyme had an apparent molecular mass of 114 kDa and was composed of two subunits of 60 kDa. The enzyme exhibited maximum activity at pH 8.5 and approximately 54° C. The K m values for fumarate and l-malate were 0.25 mM and 2.38 mM, respectively. Fumarase was inactivated by oxygen, but the activity could be restored by addition of Fe2+ and β-mercaptoethanol under anoxic conditions. EPR spectroscopy of the purified enzyme revealed the presence of a [3Fe-4S] cluster. Under reducing conditions, only a trace amount of a [4Fe-4S] cluster was detected. Addition of fumarate resulted in a significant increase of this [4Fe-4S] signal. The N-terminal amino acid sequence showed similarity to the sequences of fumarase A and B of Escherichia coli (56%) and fumarase A of Salmonella typhimurium (63%).
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    Heterologous expression of soluble methane monooxygenase genes in methanotrophs containing only particulate methane monooxygenase (1999)
    Springer
    Archives of microbiology 171 (1999), S. 364-370 
    Details
    ISSN: 1432-072X
    Keywords: Key words Heterologous expression ; Methane ; oxidation ; Methane monooxygenase ; Methanotroph ; Regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The methanotrophs Methylococcus capsulatus (Bath) and Methylosinus trichosporium OB3b contain particulate methane monooxygenase (pMMO) and soluble methane monooxygenase (sMMO) genes. Other methanotrophs such as Methylomicrobium album BG8 and Methylocystis parvus OBBP contain only pMMO genes. Although molecular genetic techniques are poorly developed in methanotrophs, sMMO genes were expressed in methanotrophs normally containing only pMMO genes. This was achieved by conjugation using broad-host-range plasmids containing the native promoter and sMMO genes from Mc. capsulatus (Bath) and Ms. trichosporium OB3b. sMMO genes derived from Ms. trichosporium OB3b were expressed in an active form in Mcy. parvus OBBP and in Mm. album BG8. Therefore, all of the genes required for active sMMO synthesis were contained on the broad-host-range plasmids and were expressed in the heterologous hosts. Constitutive synthesis of pMMO was observed in Mm. album BG8 when grown at high and low copper-to-biomass ratios, while transcription of the recombinant sMMO genes was only observed under growth conditions of low copper-to-biomass ratios. Therefore, the regulatory protein(s) for sMMO synthesis was also present on the plasmid used, or the heterologous host contained a regulatory system for sMMO. Expression of sMMO genes in methanotrophs containing only pMMO will assist further investigations on the expression and regulation of MMO genes in methanotrophs.
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    URL: http://dx.doi.org/10.1007/s002030050723
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    Charge Transfer Between Oxygen and Zirconia (1999)
    Springer
    Journal of thermal analysis and calorimetry 57 (1999), S. 875-881 
    Details
    ISSN: 1572-8943
    Keywords: charge transfer ; Kelvin probe ; oxidation ; work function ; zirconia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The extent of the surface charge, that develops during oxidation of zirconia, is determined using work function measurements for both bulk specimen and thin films. The bulk specimen of yttria-doped zirconia (10 mol%) exhibits maxima of the surface electrical effect at 373 and 973 K (130 and 280 mV, respectively) that can be considered in terms of oxygen chemisorption and oxygen non-stoichiometry. Thin film of undoped zirconia exhibits a maximum at 473 K (260 eV). Addition of yttria (10 mol%) to the thin film results in a substantial reduction of the maximum, to about 140 eV, that is shifted up to 600 K.
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    URL: http://dx.doi.org/10.1023/A:1010119014821
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    Kinetic analysis of DSC and thermogravimetric data on combustion of lignite (1996)
    Springer
    Journal of thermal analysis and calorimetry 46 (1996), S. 1657-1669 
    Details
    ISSN: 1572-8943
    Keywords: activation energy ; combustion ; differential scanning calorimetry ; kinetics ; lignite ; oxidation ; thermogravimetric analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Thermal analysis increasingly being used to obtain kinetic data relating to sample decomposition. This work involves a comparative study of several methods used to analyse DSC and TG/DTG data obtained on the oxidation of Beypazari lignite. A general computer program was developed and the methods are compared with regard to their accuracy and the ease of interpretation of the kinetics of thermal decomposition. For this study, the ratio method was regarded as the preferred method, because it permits the estimation of reaction order, activation energy and Arrhenius constant simultaneously from a single experiment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01980771
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    Inhibited Oxidation of Cumene and Polymerization of Styrene Investigated by Solution Microcalorimetry (1999)
    Springer
    Journal of thermal analysis and calorimetry 57 (1999), S. 473-486 
    Details
    ISSN: 1572-8943
    Keywords: cumene ; oxidation ; polymerization ; quinone-amine inhibitors ; solution microcalorimetry ; styrene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of solution microcalorimetry was demonstrated on two model examples – inhibited oxidation of cumene and radical polymerization of styrene. From the experimental dependences of the rate of heat release on time, the rate constants k 7 of the interaction of an inhibitor with radicals of substrate (RO 2 . or R.) in oxidation or in polymerization were determined for the set of inhibitors of N-aryl N-(2-quinone) amine series. It was shown that these compounds are weak inhibitors of oxidation of cumene and rather efficient inhibitor of polymerization of styrene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1010116024873
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    Oxidation of Styrene in a Silent Discharge Plasma (1999)
    Springer
    Plasma chemistry and plasma processing 19 (1999), S. 131-151 
    Details
    ISSN: 1572-8986
    Keywords: Styrene ; oxidation ; silent discharge ; plasma ; dielectric barrier
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract A silent discharge plasma reactor has been developed to study the oxidation of styrene vapor in argon/oxygen mixtures. A number of analytical techniques were employed to determine the destruction efficiency and to characterize the intermediate products. The destruction efficiency was measured as a function of initial styrene concentration, temperature, and energy density of the plasma. The formation of solid products was observed in most experiments. At low temperature (100°C), the solid deposit was polymeric in nature, while at high temperature (300°C) the solid appeared to be amorphous carbon. A combination of high temperature and high energy density resulted in high destruction efficiency and minimal production of solid films. The destruction efficiency vs. energy density is shown to be more complex than a simple model predicting exponential behavior. Several reasons for the discrepancy are suggested. The “e-folding” energy density for the destruction of styrene is compared to literature values for other organic compounds, measured using similar types of plasma reactors.
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    URL: http://dx.doi.org/10.1023/A:1021812201545
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    Oxidation of Dilute Benzene in an Alumina Hybrid Plasma Reactor at Atmospheric Pressure (1999)
    Springer
    Plasma chemistry and plasma processing 19 (1999), S. 383-394 
    Details
    ISSN: 1572-8986
    Keywords: Nonthermal plasma ; benzene ; Al2O3 ; BaTiO3 ; oxidation ; absorption ; atmospheric pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract The combination of plasma discharge and adsorption was examined for oxidation of dilute benzene in air in a plasma reactor packed with a mixture of BaTiO 3 pellets and porous Al 2 O 3 pellets (i.e., an alumina hybrid reactor). The oxidative decomposition of benzene was enhanced by the benzene concentrating on the Al 2 O 3 pellets. Furthermore, there was a higher selectivity to CO 2 in the products from the hybrid than from a plasma reactor packed with BaTiO 3 pellets alone. The presence of the Al 2 O 3 pellets suppressed the formation of N 2 O.
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    URL: http://dx.doi.org/10.1023/A:1021820403362
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    Oxidation and Reduction Processes During NO x Removal with Corona-Induced Nonthermal Plasma (1999)
    Springer
    Plasma chemistry and plasma processing 19 (1999), S. 421-443 
    Details
    ISSN: 1572-8986
    Keywords: Streamer corona ; NO x removal ; nonthermal plasma ; oxidation ; reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract In this paper, the NO-to-NO 2 conversion in various gaseous mixtures is experimentally investigated. Streamer coronas are produced with a dc-superimposed high-frequency ac power supply (10–60 kHz). According to NO x removal experiments in N 2 +NO x and N 2 +O 2 +NO x gaseous mixtures, it is supposed that the reverse reaction NO 2 +O→NO+O 2 may not only limit NO 2 production in N 2 +NO x mixtures, but also increase the energy cost for NO removal. Oxygen could significantly suppress reduction reactions and enhance oxidation processes. The reduction reactions, such as N+NO→N 2 +O, induce negligible NO removal provided the O 2 concentration is larger than 3.6%. With adding H 2 O into the reactor, the produced NO 2 per unit removed NO can be significantly reduced due to NO 2 oxidation. NH 3 injection could also significantly decrease the produced NO 2 via NH and NH 2 - related reduction reactions. Almost 100% of NO 2 can be removed in gaseous mixtures of N 2 +O 2 +H 2 O+NO 2 with negligible NO production.
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    URL: http://dx.doi.org/10.1023/A:1021824504271
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    Contribution to the understanding of the parabolic oxidation mechanism of dilute alloys. Part I: Oxides with metal excess or oxygen deficit (1996)
    Springer
    Oxidation of metals 46 (1996), S. 1-17 
    Details
    ISSN: 1573-4889
    Keywords: dilute alloys ; oxidation ; Wagner-Hauffe rule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Concerning the parabolic oxidation of alloys with a low content of a different valence element, we show that the Wagner-Hauffe valence approach contains some inaccuracies. This paper is devoted to the growth of an oxide MO with metal excess or oxygen deficit. The analytical processing consists in solving the differential equation connecting the point defect flux to the oxygen pressure. This equation has been solved analytically in the case where the foreign-element concentration is very high compared to that of the point defects in the pure oxide. On this assumption with a lower-valence dopant, as long as the oxide conductivity remains essentially electronic, the oxidation is limited only by the transport of ionic defects across the scale under the electric-potential gradient. Moreover, an increase of the dopant concentration may lead to an oxide exhibiting partial ionic conductivity. Consequently, the parabolic constant variations as a function of the dopant concentration is not monotonic, contrary to results published before. With a higher-valence dopant, the conductivity always remains electronic, and this result agrees with predictions based on the Wagner Hauffe approach, though the demonstrations are fundamentally different.
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    URL: http://dx.doi.org/10.1007/BF01046881
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    Effect of short-circuiting on the oxidation kinetics of copper and its doped varieties in the temperature range of 523–1073 K (1996)
    Springer
    Oxidation of metals 46 (1996), S. 73-107 
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    ISSN: 1573-4889
    Keywords: oxidation ; copper ; Li-doped copper ; Cr-doped copper ; short-circuiting ; Mott's parabola ; Wagner's parabola
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The influence of shorting circuitry attachment between metal-oxide and oxideoxygen interfaces on the oxidation kinetics of copper, lithium-doped copper (Li: 400 ppm), and chromium-doped copper (Cr: 12 ppm) have been studied in dry air $$(P_{O_2 } = 21.27kPa)$$ in the temperature range of 523–1073 K. Oxide film or scale growth under short-circuiting as well as under normal oxidation conditions conforms to the parabolic rate law. The oxidation kinetics under short-circuiting resulted in decreased rates for Cu and Li-doped Cu up to a temperature of 773 K, while Cr-doped Cu exhibited an enhancement in rate compared to its normal oxidation in the same temperature range. However, above 873 K, all three systems under shorting circuitry attachment exhibited enhanced rates compared to their normal oxidation rates in conformity to the existing theoretical model. Use of additional resistances in series in the outer short-circuit Pt path have clearly established that below 773 K Mott's fieldinduced migration plays the most important role, while at elevated temperatures Wagner's electrochemical potential-gradient factor acts as the main driving force in the scale-growth process. The results have been interpreted on the basis of average defect concentration, the electrochemical potential gradient, electrical field gradient, and transport coefficient in the Cu2O layer.
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    URL: http://dx.doi.org/10.1007/BF01046885
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    Effect of Cr, Co, and Ti additions on the high-temperature oxidation behavior of Ni3Al (1996)
    Springer
    Oxidation of metals 46 (1996), S. 109-127 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; Ni3Al base alloy ; chromium ; cobalt ; titanium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The oxidation behavior of Ni3Al+2.90 wt.% Cr, Ni3Al+3.35 wt% Co, and Ni3Al+2.99 wt.% Ti alloys was studied in 1 atm of air at 1000, 1100, and 1200°C. Isothermal tests revealed parabolic kinetics for all three alloys at all temperatures. Cyclic oxidation for 28 two-hour cycles produced little spallation at 1000°C, but caused partial spallation at 1100°C. Especially, at 1200°C severe spallation in all three alloys was observed. Although additions of Cr, Co, or Ti to Ni3Al alloys slightly increased the isothermal-oxidation resistance, the additions tended to decrease the cyclic-oxidation resistance. The major difference in the oxidation of the three alloys compared with the oxidation of pure Ni3Al alloys was the existence of small α-Al2O3 particles in the middle of the α-Al2O3 scale and the formation of irregularly shaped Kirkendall voids at the alloy-scale interface.
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    An in vitro study on the role of metal catalyzed oxidation in glyeation and crosslinking of collagen (1999)
    Springer
    Molecular and cellular biochemistry 194 (1999), S. 257-263 
    Details
    ISSN: 1573-4919
    Keywords: glycation ; oxidation ; collagen ; diabetes ; free radicals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The present investigation was carried out to understand the effect of metal catalyzed oxidation on glycation and crosslinking of collagen. Tail tendons obtained from rats weighing 200-225 g were incubated with glucose (250 mM) and increasing concentrations of copper ions (5, 25, 50 and 100 μM) under physiological conditions of temperature and pH. Early glycation, crosslinking and late glycation (fluorescence) of collagen samples were analyzed periodically. Early glycation was estimated by phenol sulfuric acid method, and the crosslinking was assessed by pepsin and cyanogen bromide digestion. A concentrationdependent effect of metal ions on the rate of glycation and crosslinking of collagen was observed. Tendon collagen incubated with glucose and 100 μM copper ions showed 80% reduction in pepsin digestion within seven days, indicating extensive crosslinking, whereas collagen incubated with glucose alone for the same period showed only 7% reduction. The presence of metal ions in the incubation medium accelerated the development of Maillard reaction fluorescence on collagen, and the increase was dependent on the concentration of metal ions used. The metal chelator Diethylene triamine penta-acetate significantly prevented the increase in collagen crosslinking by glucose and copper ions. Free radical scavengers benzoate and mannitol effectively prevented the increased crosslinking and browning of collagen by glucose. The results indicate that the metal catalyzed oxidation reactions play a major role in the crosslinking of collagen by glucose. It is also suggested that the prevention of increased oxidative stress in diabetes may prevent the accelerated advanced glycation and crosslinking of collagen.
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    URL: http://dx.doi.org/10.1023/A:1006988719374
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    Influence of external mechanical loadings (creep, fatigue) on oxygen diffusion during nickel oxidation (1996)
    Springer
    Oxidation of metals 45 (1996), S. 153-181 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; 18O diffusion ; nickel ; stress effects on diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract This study deals with the influence of various mechanical loadings (fatigue, creep, creep-fatigue) on oxygen diffusion in a particular system, oxidizing nickel. A distinction between the behavior of the oxide layer and underlying nickel was noted during the first step of oxidation at 550°C, in PO 2=1 atm. Mechanical loading causes a decrease of the oxygen mobility through the oxide scale (factor of 103). The oxide thicknesses on nickel undergoing mechanical loadings are different than for an unloaded sample, due to distinct contributions of the oxygen and nickel fluxes in the growing oxide. In the substrate, the ingress of oxygen becomes easier with a constant tensile load (creep). The intergranular-oxygen diffusion coefficient, Di, is increased by a factor of 102 with respect to other samples. In creep, oxygen diffusion takes place along grain boundaries of a structure with smaller grains than in unstrained Ni. A short fatigue period during creep-fatigue decreases the sensitivity of nickel to intergranular-oxygen diffusion.
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    URL: http://dx.doi.org/10.1007/BF01046824
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    Attenuation of sugar cataract by ethyl pyruvate (1999)
    Springer
    Molecular and cellular biochemistry 200 (1999), S. 103-109 
    Details
    ISSN: 1573-4919
    Keywords: sugar cataract ; dulcitol ; glycation ; oxidation ; pyruvate ; ethyl pyruvate ; attenuation effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Studies describe an attenuation of sugar cataract formation by topical administration of ethyl pyruvate. Cataract formation was induced by feeding young rats a 30% galactose diet. Mature cataracts appeared in about thirty days. Instillation of the eye drops containing 5% ethyl pyruvate decelerated the process significantly. Biochemically, the effect was reflected by lowering in the contents of dulcitol and glycated proteins. The ATP levels were also higher in comparison to the placebo treated group. The effects are hence attributable to the effect of pyruvate in inhibiting dulcitol synthesis and protein glycation, in addition to its antioxidant properties and metabolic support. The use of esterified pyruvate instead of the unesterified pyruvate was preferred because of its greater penetration through the cornea and consequently a higher concentration attained in the aqueous humor.
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    Ellipsometric study of a palladium catalyst during the oxidation of carbon monoxide and methane (1999)
    Springer
    Topics in catalysis 8 (1999), S. 35-43 
    Details
    ISSN: 1572-9028
    Keywords: ellipsometry ; carbon monoxide ; methane ; palladium ; palladium oxide ; oxidation ; oscillations ; catalyst
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Spectroscopic ellipsometry is used to monitor the surface of a thick Pd‐film catalyst during the oxidation of either carbon monoxide or methane. Dense PdO layers form under sufficiently lean conditions (excess oxygen) for both reactions. A stable metal surface exists in the case of CO, but a very porous PdO layer develops in the case of methane, under rich conditions. There is a large hysteresis in the conditions for PdO formation in the case of CO oxidation. Spontaneous oscillations in catalytic activity and Pd‐surface composition occur for both reactions, the higher activities corresponding to O‐atom‐rich or PdO‐rich surfaces for CO or methane oxidation, respectively.
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    Laser Raman spectroscopy – a powerful tool for in situ studies of catalytic materials (1999)
    Springer
    Topics in catalysis 8 (1999), S. 45-55 
    Details
    ISSN: 1572-9028
    Keywords: Raman spectroscopy ; surface‐enhanced Raman spectroscopy ; oxidation ; synergy effects ; oxygen exchange ; oxidative coupling of methane ; nitric oxide decomposition ; methanol oxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Advantages and limitations of laser Raman spectroscopy (LRS) as an in situ vibrational spectroscopy for the study of catalytic materials and surfaces under working conditions are discussed. Measurements can be carried out at temperatures as high as 1200 K in controlled atmospheres. Modern instrumentation permits time resolutions in the sub‐second regime for materials with high Raman cross sections. Transient studies are thus possible. Several examples are presented of in situ LRS studies including the phase analysis of bismuth molybdate and VPO oxidation catalysts, synergy effects and oxygen exchange in Sb2O3/MoO3 oxide mixtures, intermediates in oxidative coupling of methane, NO decomposition on Ba/MgO catalysts, and transient SERS studies of partial oxidation of methanol on Ag single crystal surfaces and of the reduction of oxide overlayers on electrodeposited Rh layers.
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    A study on the oxidation characteristics of cast irons containing aluminum (1996)
    Springer
    Oxidation of metals 45 (1996), S. 109-131 
    Details
    ISSN: 1573-4889
    Keywords: Fe−Al−C ; Fe−Al−Si−C ; inoculation ; scale ; characterization ; oxidation ; high temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Isothermal-oxidation characteristics of cast irons containing aluminum (5–15% Al) from 700 to 1000°C in air have been studied. In addition to massgain measurements, the morphology and composition of the oxide scales have been examined by SEM-EDX system and XRD analysis. A normal Fe−5Al−C alloy does not develop protective, adherent scales. Even the addition of misch metal and calcium silicide to such an alloy does not improve its oxidation resistance. But aluminum cast iron develops considerable oxidation resistance only when a sufficient quantity of silicon is also present in the alloy. Treatment of the alloy with misch, metal and calcium silicide together assists in protective scale formation. Among the alloys investigated Fe−15Al−Si−C treated with misch metal and calcium silicide shows minimum oxidation at 1000°C.
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    Corrosion of iron in sulfur dioxide at 0.1 MPa (1996)
    Springer
    Oxidation of metals 45 (1996), S. 469-486 
    Details
    ISSN: 1573-4889
    Keywords: iron ; sulfur dioxide ; oxidation ; tracer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The reaction of iron with sulfur dioxide at 0.1 MPa and 1073 K was studied. The composition and morphology of the scales, transport phenomena occurring in the growing scales, and kinetics of the process were investigated. Scanning electron microscopy and various techniques of X-ray analysis were used. The transport phenomena were studied by marker and by radiotracer techniques. The scales were composed of sulfide and oxides and grew by the outward diffusion of metal. It was concluded that the process initially took place through the reaction of iron with sulfur dioxide molecules. During the next stage of the process the reaction with sulfur dioxide molecules as well as with oxygen molecules is possible.
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    High-temperature corrosion of Ti and Ti-6Al-4V alloy (1996)
    Springer
    Oxidation of metals 45 (1996), S. 507-527 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; sulfidation ; oxides ; sulfides ; Ti ; Ti-6Al-4V alloy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Pure titanium and Ti-6Al-4V were exposed at 750°C in an H2/H2O/H2S PO 2≈10−18 Pa and PS 2≈10−1 Pa), H2/H2O (PO 2≈10−18 Pa) and air environments for up to 240 hr. The corrosion kinetics, obtained by the discontinuous gravimetric method, showed that the sulfidation/oxidation kinetics were linear for Ti and linear-parabolic for Ti-6Al-4V in the H2/H2O/H2S environment. Both materials obeyed parabolic rate laws in the H2/H2O atmosphere after a transient period, and linear-parabolic rate laws in air. After exposure to the H2/H2O/H2S atmosphere, the titanium specimen displayed a double scale of TiO2 with an intervening TiS2 film between the double-layered scale of TiO2 and the substrate. Ti-6Al-4V also contained a double layer of TiO2 together with a stratum consisting of Al2S3, TiS2 and vanadium sulfide at the junction of the inner TiO2 layer and substrate. Some Al2O3 precipitated in the external portion of the outer TiO2 layer. Following oxidation in the low-PO 2 atmosphere a double-layered oxide of TiO2 scale formed on both Ti and Ti-6Al-4V. The scale on Ti-6Al-4V also contained an α-Al2O3 film situated between the outer and inner (TiO2) layers. For both materials, multilayered-scale formation characterized air oxidation. In detail a multilayered oxide scale of TiO2 formed on the air-oxidized Ti, while a multilayered oxide scale with alternating layers of Al2O3/TiO2 developed on Ti-6Al-4V oxidized in air.
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    Mixed oxidant corrosion in nonequilibrium gasifier environments (1996)
    Springer
    Oxidation of metals 45 (1996), S. 487-505 
    Details
    ISSN: 1573-4889
    Keywords: sulfidation ; oxidation ; gasification ; austenitic steel alloys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The major use of high-temperature steel alloys in gasifiers is in heat exchangers for cooling hot syngas, consisting mainly of CO and H2 with lesser amounts of H2O and CO2 and minor quantities of H2S and HCl. Metal temperatures range from 250 to 600°C, gas temperatures from 250 to 1200°C. Because of rapid cooling the composition of the gas does not change with temperature. Therefore the gas is not in equilibrium at the metal surface. Calculations show that such gases have lower oxygen and sulfur pressures than equilibrated gases at the same temperature. This makes the results of previous laboratory studies less appropriate for predicting mixed oxidant corrosion in gasifiers. For this reason the present study was carried out using nonequilibrium gas mixtures, similar to gases, produced in entrained-slagging gasifiers. Most corrosion experiments were carried out at 540°C, as this is a common temperature for superheaters and hot-gas cleanup systems. Iron-base model alloys containing 35% Ni, 20% Cr, and various minor alloying additions were studied. Three corrosion regimes were identified over the range of conditions studied, depending on the sulfur-to-oxygen pressure ratio of the gas and the alloy composition. At high PS 2/PO 2 ratios a somewhat protective FeCr2S4 scale formed on all alloys. Below this layer internal oxidation and sulfidation occurred at a slow rate. At lower PS 2/PO 2 ratios nonprotective Fe(Ni, Cr)S external scales formed. These allow rapid internal oxidation of the chromium in the alloy, resulting in high corrosion rates. Under the same conditions very low corrosion rates are obtained when silicon is added to the alloy, because the presence of SiO2 precipitates makes the internal-oxidation layer protective. Thus, the same corrosion model is operative in all three corrosion regimes: external sulfidation of iron and nickel, together with internal oxidation of chromium and other strong-oxide formers.
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    TEM investigations of the early stages of TiAl oxidation (1996)
    Springer
    Oxidation of metals 46 (1996), S. 255-285 
    Details
    ISSN: 1573-4889
    Keywords: electron diffraction ; intermetallic ; oxidation ; TEM ; titanium aluminide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The early stages of TiAl oxidation at 900°C and 1000°C in air have been investigated by transmission electron microscopy (TEM). The investigations revealed that at the beginning of oxidation, i.e., after 4 min, TiO2 and Al2O3 grow in a preferential orientation on the γ-TiAl substrate. After 4 h of oxidation an oxide scale structure can already be found similar to that known from long-term oxidation. In addition, besides α-Al2O3, the formation of a second aluminum oxide phase and of titanium nitrides is observed. The processes at the metal-oxide interface of oxidation in the early stages, consisting of a repeated cycle of Al2O3 formation, Al2O3 dissolution, outward migration of Al through the scale, and reprecipitation of Al2O3 in the outer scale, are described by a model. The four stages observed in the kinetics of TiAl oxidation are explained on the basis of the results obtained and the structure of the oxide scale.
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    URL: http://dx.doi.org/10.1007/BF01050799
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    The corrosion of pure niobium in oxidizing, sulfidizing, and oxidizing-sulfidizing gas mixtures at 600–800°C (1996)
    Springer
    Oxidation of metals 46 (1996), S. 287-297 
    Details
    ISSN: 1573-4889
    Keywords: pure niobium ; oxidation ; sulfidation ; oxidation-sulfidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The corrosion of pure niobium has been studied at 600–800°C in various environments as part of a study of the corrosion resistance of its alloys with iron, cobalt, and nickel to atmospheres of low-oxygen and/or high-sulfur activities. The results have shown that not only the sulfidation but also the corrosion in mixed atmospheres and particularly the oxidation under low oxygen pressures of pure niobium are quite slow, with kinetics rather similar in the three types of gas mixtures used. The good corrosion resistance of niobium to attack by oxygen under low pressures is quite interesting because this element is corroded very rapidly by oxygen under high oxygen pressures, due to the formation of the nonprotective highest oxide Nb2O5 as a main corrosion product.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01050800
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    The oxidation behavior of Fe-20Cr alloy foils in a synthetic exhaust-gas atmosphere (1996)
    Springer
    Oxidation of metals 46 (1996), S. 335-364 
    Details
    ISSN: 1573-4889
    Keywords: Fe−Cr ; oxidation ; exhaust gas ; oxide adherence ; titanium ; rare earths
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Oxidation tests of rare-earth-modified and Ti-modified Fe−20Cr alloy foils, which are under consideration for catalytic converter supports, were performed in a synthetic exhaust-gas atmosphere (N2+H2O+CO2) between 900°C and 650°C. Between 900°C and 750°C, the rare earths had no effect on oxide growth rates while Ti increased growth rates. Oxide growth rates for the rareearth alloys at 800°C and 750°C are much lower than those found in the literature for oxidation of Fe−Cr alloys or pure Cr in O2-rich atmospheres. The slow growth rates for the rare-earth alloys agree with literature data for oxidation of stainless steels containing 〉20% Cr in wet atmospheres and are caused by growth of an oxide scale only one grain thick. At temperatures ≤700°C, Fe−20Cr alloys grow massive Fe oxides; however, this can be suppressed by adding rare earths or Ti. To ensure good oxide adherence, free sulfur must be eliminated in the alloy by tying it up with a reactive-element addition. Both Ti and the rare earths can be used to tie up S, but the rare earths are more effective. For converter applications, the optimum alloy composition may contain rare earths for good oxide adherence and a small amount of Ti to suppress growth of Fe-rich oxides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01048635
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    Transient oxidation in Fe-Cr-Ni alloys: A Raman-scattering study (1996)
    Springer
    Oxidation of metals 46 (1996), S. 365-381 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; steel ; Raman ; scale ; transient oxides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Using Raman scattering we have investigated the oxidation, in air, of the Fe-Cr-Ni stainless steels Fe-25Cr-20Ni, Fe-25Cr-20Ni-3Zr, and Fe-24Cr-3Zr (wt.%) as a function of temperature in the range 300 to 1000°C. The Raman technique is very sensitive to, and provides a clear identification of, the oxides Fe2O3 and Cr2O3. However, the technique is insensitive to NiO, FeO, and does not give a clear identification of spinels. The Fe−Cr−Ni alloys form chromia scales at temperatures greater than ∼800°C. At lower oxidation temperatures, transient phases are observed. With a 1-h heat treatment at 300°C, we observe the formation of an unidentified scale; we speculate that it is either amorphous or consists of disordered spinel(s). Near 400°C we begin to observe hematite (Fe2O3). The intensity of the Fe2O3 signal increases with temperature to ∼600°C and then decreases, being largely replaced by the signal from Cr2O3. The thickness of the Cr2O3 scale increases with temperature up to ∼1000°C above which spallation becomes apparent. Spinel phases also apparently persist in the scale to 1000°C.
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    URL: http://dx.doi.org/10.1007/BF01048636
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    The steady-State corrosion kinetics of two-phase binary alloys forming the most-stable oxide (1996)
    Springer
    Oxidation of metals 46 (1996), S. 383-398 
    Details
    ISSN: 1573-4889
    Keywords: high temperatures ; binary alloys ; two-phase alloys ; oxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The steady-state kinetics in the high-temperature oxidation of binary A-B alloys containing a mixture of the conjugated solid solutions of B in A (alpha phase) and A in B (beta phase) with exclusive formation of the most-stable oxide BOv have been examined, assuming that the external scale grows on top of a subsurface layer of alpha phase. The results obtained are compared with the corresponding behavior of alloys which are single phase in the whole range of composition. Under identical values of all the parameters involved the concentration of B at the alloy-scale interface is smaller for two-phase than for single-phase alloys under the same concentration of B in the alloy as a result of the restricted flux of B through the alpha-phase layer. As a consequence of this, the two-phase alloys corrode more slowly than single-phase alloys and this difference increases as the solubility of B in the alpha phase decreases. Finally, the simultaneous formation of BOv both externally and as internal oxide is more likely for two-phase than for single-phase materials.
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    URL: http://dx.doi.org/10.1007/BF01048637
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    An analysis of the internal oxidation of binary M-Nb alloys under low oxygen pressures at 600–800°C (1996)
    Springer
    Oxidation of metals 46 (1996), S. 441-463 
    Details
    ISSN: 1573-4889
    Keywords: niobium alloys ; oxidation ; high temperatures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The corrosion of M−Nb alloys based on iron, cobalt, and nickel and containing 15 and 30 wt% Nb has been studied at 600–800°C under low oxygen pressures (10−24 atm at 600°C and 10−20 atm at 700–800°C). Except for the Co−Nb and Ni−Nb alloys corroded at 800°C, which formed external scales of niobium oxides, corrosion under low O2 pressures produced an internal oxidation of niobium. This attack was much faster than expected on the basis of the classical theory. Furthermore, the distribution of the internal oxide in the alloys containing two metal phases was very close to that of the Nb-rich phase in the original alloys. These kinetic, microstructural, and thermodynamic aspects are examined by taking into account the effects of the limited solubility of niobium in the various base metals and of the two-phase nature of the alloys.
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    URL: http://dx.doi.org/10.1007/BF01048640
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    The effect of oxygen concentration on the oxidation of low-carbon steel in the temperature range 1000 to 1250°C (1996)
    Springer
    Oxidation of metals 46 (1996), S. 423-440 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; scaling ; surface temperature ; heat of reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract This paper describes the oxidation behavior of low-carbon steel samples in binary gas mixtures of oxygen and nitrogen, at oxygen concentrations ranging between 1% and 15% and temperatures ranging between 1000 and 1250°C. Sample weight gains versus time were analyzed, along with measurements and calculations of sample heating rates due to exothermic heat of reaction at the sample surface. It was found that initial rates of oxidation depended on oxygen content in the gasmixture and that these reaction rates were linear up to oxide thicknesses of 0.4 to 0.5 mm. Calculations of linear oxidation rate constants based on equations for mass transport of oxygen in the gas mixture to the sample surface showed good agreement with those measured experimentally, indicating that the initial period of oxidation is controlled by the mass transport of oxygen to the reaction interface. The linear rate constants showed little dependency on temperature, an activation energy of approximately 17kJ/mole being obtained. Measurements of sample surface temperatures have shown that within this linear-oxidation regime, interfacial temperatures of the samples increase with increasing oxygen contents in the gas mixture, owing to exothermic heats of oxidation. Subsequent oxidation kinetics were found to be parabolic. Measured parabolic rates constants were in good agreement with previous investigations, with activation energy values of approximately 127kJ/mole.
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    URL: http://dx.doi.org/10.1007/BF01048639
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    Effect ofθ-alumina formation on the growth kinetics of alumina-forming superalloys (1996)
    Springer
    Oxidation of metals 46 (1996), S. 465-480 
    Details
    ISSN: 1573-4889
    Keywords: ODS Alloy ; oxidation ; SIMS ; microstructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Alumina-forming ODS superalloys are excellent oxidation-resistant materials. Their resistance relies upon the establishment of a stable, slow-growing, and adherent α-alumina. In the present investigation, these alloys exhibited unstable and relatively less adherent θ-alumina phase, which increased the oxidation rate in the transient stage and converted into α-alumina in the later part of the exposure. The oxide-growth process was found to depend upon various parameters such as temperature, time, and presence of an active elecment in the superalloy. Characterization carried out by XRD, SEM/EDAX, and AES on oxidized ODS and non-ODS alloys demonstrated a significant influence of the active element, Y, on the transformation of θ- to α-alumina. SIMS analysis of two-stage oxidation at 900°C for two different durations evidently showed that the change in the transport process is due to θ-to-α-alumina transformation. On the basis of these results, a new and consistent mechanism is proposed to explain the influence of θ-alumina and its transformation on growth kinetics and the effect of yttrium on the transformation leading to good scale adherence and oxidation resistance.
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    URL: http://dx.doi.org/10.1007/BF01048641
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    Tailoring Silicon Oxycarbide Glasses for Oxidative Stability (1999)
    Springer
    Journal of sol gel science and technology 14 (1999), S. 75-86 
    Details
    ISSN: 1573-4846
    Keywords: silicon oxycarbide ; BlackglasTM ; ceramic matrix composites ; 29Si NMR ; oxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract BlackglasTM polysiloxane systems produce silicon oxycarbide glasses by pyrolysis in inert atmosphere. The silicon oxycarbides evidence oxidative degradation that limits their lifetime as composite matrices. The present study characterizes bonding rearrangements in the oxycarbide network accompanying increases in pyrolysis temperature. It also addresses the changes in susceptibility to oxidation due to variations in the distribution of Si bonded species obtained under different processing conditions. The study is carried out using 29Si nuclear magnetic resonance (NMR) spectroscopy and a design of experiments approach to model the oxidation behavior. The NMR results are compared with those obtained by thermogravimetric analysis (TGA). Samples pyrolyzed under inert conditions are compared to those pyrolyzed in reactive ammonia environments.
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    URL: http://dx.doi.org/10.1023/A:1008727914900
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    Insights into the Oxidation Chemistry of SiOC Ceramics Derived from Silsesquioxanes (1999)
    Springer
    Journal of sol gel science and technology 14 (1999), S. 49-68 
    Details
    ISSN: 1573-4846
    Keywords: silicon oxycarbide ; oxidation ; silsesquioxane ; preceramic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We have undertaken a systematic study of the oxidation chemistry for a range of SiOC ceramics derived from silsesquioxane polymeric precursors. This study examines the oxidation for 500 hours at 600, 800, 1000 and 1200°C for four SiOC powders. The material changes upon oxidation were characterized qualitatively by color change and optical microscopy and quantitatively by weight and composition change. In this study we employ a very easy method that uses the weight change upon oxidation and a carbon analysis after oxidation to arrive at the composition of the oxidized SiOC. Combined these qualitative and quantitative techniques have shown that on oxidation at 800 and 600°C the SiOC composition is more rapidly changed to that of silica than oxidation over the same time frame at 1000 or 1200°C. The data indicates that this difference is due to the relative rates of oxidation of the excess carbon versus the Si—C bonds in the SiOC. At lower temperatures initially the carbon oxidation predominates which leads to higher porosity throughout the material and an increase in the surface area with eventually ‘complete’ oxidation to silica. At higher temperatures the Si—C bond oxidation rate is comparable to the rate of oxidation of carbon. This allows a silica-like surface to build up on the SiOC, which slows all subsequent reactions due to the necessity to diffuse O2 in and COx out of the bulk. Under these oxidation conditions materials that originally contain high amounts of excess carbon are more quickly oxidized to silica than those that contain minimal amounts of excess carbon, as confirmed by elemental analysis and optical microscopy. Regardless of the time or temperature of the oxidation conditions no materials were found to be completely stable to oxidation. SiOC materials with low levels of excess carbon showed the best resistance to change upon oxidation.
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    URL: http://dx.doi.org/10.1023/A:1008723813991
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    Mössbauer effect study of anapaite, Ca2Fe2+(PO4)2 · 4H2O, and of its oxidation products (1999)
    Springer
    Physics and chemistry of minerals 26 (1999), S. 506-512 
    Details
    ISSN: 1432-2021
    Keywords: Key words Anapaite ; Mössbauer spectroscopy ; oxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Abstract Mössbauer spectra (MS) of anapaite (Ca2 Fe2+(PO4)2 · 4H2O) and of a sample after being immersed in a 4% H2O2 solution at room temperature (RT) over 12 days (hereafter an4ox) were collected at temperatures in the range 4.2 to 420 K and 11 to 300 K respectively. All MS consist of symmetrical doublets, hence magnetic ordering was not observed. The temperature dependencies of the Fe2+ centre shifts of anapaite and an4ox were analysed with the Debye model for the lattice vibrations. The characteristic Mössbauer temperatures were found as 370 K ± 25 K and 340 K ± 25 K, and the intrinsic isomer shifts as 1.427 ± 0.005 mm/s and 1.418 ± 0.005 mm/s respectively. From the external-field (60 kOe) MS recorded at 4.2 and 189 K for the non-treated sample, the principal component V zz of the electric field gradient (EFG) is determined to be positive and the asymmetry parameter η ≈ 0.2 and 0.4 respectively. The temperature variations of the quadrupole splittings, ΔE Q(T), cannot be interpreted on the basis of the thermal population of the 5 D electronic levels resulting from the tetragonal compression of the O6 co-ordination. The low-temperature linear behaviour of ΔE Q(T) is attributed to a strong orbit-lattice coupling. A field of 60 kOe applied to anapaite at 4.2 K produces magnetic hyperfine splitting with effective hyperfine fields of −136, −254 and −171 kOe along the principal axes Ox, Oy and Oz of the EFG tensor respectively. Additional oxidation treatments in solutions with various H2O2 concentrations up to 20% and subsequent Mössbauer experiments at room temperature, have revealed that the anapaite structure is not sensitive to oxidation since eventually only a small amount of Fe2+ (∼6.5%) is converted into Fe3+.
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    URL: http://dx.doi.org/10.1007/s002690050213
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    Acid-catalyzed formation of free radicals in the reaction of hydroperoxides with ketones (1996)
    Springer
    Russian chemical bulletin 45 (1996), S. 340-345 
    Details
    ISSN: 1573-9171
    Keywords: oxidation ; acid catalysis ; free radicals ; acetonitrile ; p-toluenesulfonic acid ; tert-butyl hydroperoxide ; cyclohexanone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of formation of free radicals in the cyclohexanone (CH)-tert-butylhydroperoxide (TBHP)-para-toluenesulfonic acid (PTSA) system in acetonitrile was studied. The stoichiometry of the reaction corresponds to the consumption of two TBHP molecules per ketone molecule, whereas the yield of free radicals is -20 % based on the TBHP reacted.
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    New heterocyclic system based on vinylsulfonylfluorobenzene and X-ray structural study of this compound (1996)
    Springer
    Russian chemical bulletin 45 (1996), S. 414-416 
    Details
    ISSN: 1573-9171
    Keywords: 1,2,4,5-tetrafluoro-3,6-bis(vinylthio)benzerne ; 1,2,4,5-tetrafluoro-3,6bis(vinylsulfonyl)benzene ; 5,6-difluorobenzo-[a,d]-bis(3,3′-dihydro-1,1′-sulfonylallyl-4,4′-perhydroazine) ; oxidation ; allylamine ; X-ray structural study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Oxidation of 1,2,4,5-tetrafluoro-3,6-bus (vinylthio)benzene (1) affords 1,2,4,5-tetra fluoro3,6-bis(vinylsulfonyl)benzene (2) in 65 % yield. The reaction of compound 2 with allylamine gives a new heterocyclic compound, 5,6-difluorobenzo-[a,d]-bis(3,3′-dihydro-l,l′-sulfonylallyl-4,4′-perhydroazine) (3). This compound is the product of nucleophilic addition at the vinylsulfonyl group and intramolecular replacement of fluorine atoms of the benzene ring. The structure of compound 3 has been established by X-ray structural study.
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    URL: http://dx.doi.org/10.1007/BF01433984
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    The influence of low-temperature oxidation of active carbons by nitric acid on their physicochemical properties (1996)
    Springer
    Russian chemical bulletin 45 (1996), S. 1071-1077 
    Details
    ISSN: 1573-9171
    Keywords: active carbons ; oxidation ; surface chemistry ; n-hexane ; water ; methanol ; adsorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The influence of oxidation by nitric acid on the character of oxygen-containing functional surface groups and porous structure of active carbons is considered. Adsorption properties of the initial and oxidized carbons are studied using adsorption isotherms of vapor of n-hexane and polar substances (water and methanol).
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    URL: http://dx.doi.org/10.1007/BF01431592
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    Heat release kinetics in the reaction of decane with nitric acid (1996)
    Springer
    Russian chemical bulletin 45 (1996), S. 1883-1888 
    Details
    ISSN: 1573-9171
    Keywords: decane ; nitric acid ; nitrogen dioxide ; oxidation ; kinetics ; mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of the reaction of decane with nitric acid (25.07–75.53 %) at 57.8 to 119 °C in an acid-decane-gas triphasic system was studied. The main contribution to the rate of heat release is made by the oxidation of decane with nitrogen dioxide in the organic phase proceedingvia the mechanism of a degenerate branched-chain reaction. Nitration plays the role of a chain termination reaction. The acid phase is the source of NO2, whose content increases with oxidation. The equilibrium of the nitrogen dioxide distribution in the triphasic system was analyzed. The kinetic law of the reaction, the dependences of the reaction constants of the initial and catalytic stages on temperature and the acid phase composition were determined. The results allow one to calculate the rate of heat release in the decane-HNO3 system under any conditions of the process.
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    Phenazinee di-N-oxide radical cation and its reactions with hydrocarbons (1996)
    Springer
    Russian chemical bulletin 45 (1996), S. 1889-1895 
    Details
    ISSN: 1573-9171
    Keywords: phenazine di-N-oxide ; radical cation ; hydrocarbons ; oxidation ; mechanism ; O2 effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The absorption spectra of phenazine di-N-oxide radical cation (OPO+·) in dichloromethane were recorded by the spectroelectrochemical method in the range from 300 to 700 nm. The reactions of the electrochemically generated OPO+· withpara-substituted toluenes, ethylbenzene, and cumene were studied. Using differential cyclic voltammetry, relative rate constants of reactions of OPO+· with substrates were determined; their correlations with σ+ para constants of substituents gives p = -2.7, which attests to the nonradical character of the reaction of OPO+· with RH. This conclusion is confirmed by the study of the effect of O2 on oxidation of ethylbenzene and cumene.
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    Interaction of diphenyl sulfide with sulfuryl chloride (1996)
    Springer
    Russian chemical bulletin 45 (1996), S. 2668-2669 
    Details
    ISSN: 1573-9171
    Keywords: diphenyl sulfide ; sulfuryl chloride ; oxidation ; chlorination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The reaction of diphenyl sulfide with sulfuryl chloride was studied. Depending on the reaction conditions, it occurs either as chlorination of the aromatic ring or as oxidation to give sulfoxide.
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    URL: http://dx.doi.org/10.1007/BF01431143
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    Formation of isomeric iodohydrins from terminal alkenes upon oxidation by a RuCl3-NaIO4 system (1996)
    Springer
    Russian chemical bulletin 45 (1996), S. 2813-2815 
    Details
    ISSN: 1573-9171
    Keywords: alkenes ; catalysis ; oxidation ; iodohydrins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract RuCl3-catalyzed periodate oxidation of alkenes affords isomeric iodohydrins.
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    URL: http://dx.doi.org/10.1007/BF01430649
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    Universal Correlation of Nitrogen 1s and Oxygen 1s Photoelectron Binding Energies with Chemical Composition in Nitrogen-Containing Plasma Polymers (1999)
    Springer
    Plasmas and polymers 4 (1999), S. 283-307 
    Details
    ISSN: 1572-8978
    Keywords: Plasma polymers ; oxidation ; XPS ; photoelectron binding energy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract The incorporation of oxygen into nitrogen-containing plasma deposited polymers was studied by X-ray Photoelectron Spectroscopy (XPS). As the oxygen content of the plasma polymer increased, the binding energy of the N 1s photoelectrons increased. Conversely, the binding energy of the O 1s photoelectrons was inversely proportional to the nitrogen content of the plasma polymer. The data from a large number of samples all obeyed the same “universal” correlations of photoelectron binding energy versus chemical composition. The data were described by the same curve regardless of whether the oxygen was incorporated rapidly into the thin film during plasma deposition or whether the oxygen was added slowly during spontaneous oxidation of the film in air. This implies that the same thermodynamic principles of radical reactions governed the addition of oxygen to the plasma polymer. The shift in the O 1s and N 1s photoelectron binding energies as a function of chemical composition was used to monitor the proximity of nitrogen and oxygen. By contrasting the experimental data with a simple binomial model which described the random addition of oxygen to a lattice containing carbon and nitrogen, we were able to show that oxygen was preferentially added near nitrogen-containing groups in plasma polymers.
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    URL: http://dx.doi.org/10.1023/A:1021831527895
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    Clinical and pharmacokinetic phase I trial of oral dimethylaminoetoposide (NK611) administered for 21 days every 35 days (1996)
    Springer
    Investigational new drugs 14 (1996), S. 379-386 
    Details
    ISSN: 1573-0646
    Keywords: NK611 ; dimethylaminoetoposide ; phase I ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have conducted a clinical and pharmacokinetic trial of the novel podophyllotoxin derivative NK611 administered orally for 21 consecutive days. The treatment was repeated every 35 days. Eighteen patients were included into the study, all of whom were eligible. Due to early progression of tumor disease in two patients, 16 patients were évaluable for toxicity [7 female, 9 male, median age 64 years (range: 44 to 73)]. Dose escalation steps were 5 mg/day [105 mg per cycle (pc)], 10 mg/day (210 mg pc), 12.5 mg/day (265 mg pc) and 15 mg/day (315 mg pc). A total of 37 courses was administered. Toxicity was evaluated using NCI-CTC criteria. Granulocytopenia was the main hematologic toxicity. Other hematologic toxicities were sporadic. Non-hematologic toxicities were mild and consisted of grade 1 nausea and grade 2 alopecia. Pharmacokinetic analyses were performed in six patients each treated with 10 mg/day and 12.5 mg per day, and in one patient treated with 15 mg/day. Using a two-compartment model, t1/2α ranged from 0.47 to 1.54 h and t1/2β from 2.0–11.6 h. Mean values for C max and AUC were 1.47 ± 0.331 μg/ml and 13.67±3.81 μg/ml·h. No objective tumor responses were observed. However, one patient with metastatic breast cancer had stable disease for twelve months. We conclude that the Maximum Tolerated Dose of NK611 administered daily for 21 consecutive days is 12.5 mg/day. The Dose-Limiting Toxicity is granulocytopenia. The recommended dose for further clinical Phase II studies is 10 mg/day.
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    A human capecitabine excretion balance and pharmacokinetic study after administration of a single oral dose of 14C-labelled drug (1999)
    Springer
    Investigational new drugs 17 (1999), S. 49-56 
    Details
    ISSN: 1573-0646
    Keywords: pharmacokinetics ; capecitabine ; 5-fluorouracil ; phase I trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract An excretion balance and pharmacokinetic study was conducted in cancer patients with solid tumors who received a single oral dose of capecitabine of 2000 mg including 50 μ Ci of 14C-radiolabelled capecitabine. Blood, urine and fecal samples were collected until radioactive counts had fallen to below 50 dpm/mL in urine, and levels of intact drug and its metabolites were measured in plasma and urine by LC/MS-MS (mass spectrometry) and 19F-NMR (nuclear magnetic resonance) respectively. Based on the results of the 6 eligible patients enrolled, the dose was almost completely recovered in the urine (mean 95.5%, range 86–104% based on radioactivity measurements) over a period of 7 days after drug administration. Of this, 84% (range 71–95) was recovered in the first 12 hours. Over this time period, 2.64% (0.69–7.0) was collected in the feces. Over a collection period of 24–48h, a total of 84.2% (range 80–95) was recovered in the urine as the sum of the parent drug and measured metabolites (5′-DFCR, 5′-DFUR, 5-FU, FUH2, FUPA, FBAL). Based on the radioactivity measurements of drug-related material, absorption is rapid (tmax 0.25–1.5 hours) followed by a rapid biphasic decline. The parent drug is rapidly converted to 5-FU, which is present in low levels due to the rapid metabolism to FBAL, which has the longest half-life. There is a good correlation between the levels of radioactivity in the plasma and the levels of intact drug and the metabolites, suggesting that these represent the most abundant metabolites of capecitabine. The absorption of capecitabine is rapid and almost complete. The excretion of the intact drug and its metabolites is rapid and almost exclusively in the urine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006263400888
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  • 93
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    A Sensitive Docetaxel Assay in Plasma by Solid-Phase Extraction and High Performance Liquid Chromatography – UV Detection: Validation and Suitability in Phase I Clinical Trial Pharmacokinetics (1999)
    Springer
    Investigational new drugs 17 (1999), S. 325-333 
    Details
    ISSN: 1573-0646
    Keywords: docetaxel ; plasma assay ; clinical trials ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have developed a specific and sensitive method aiming atdocetaxel (Taxotere®) determination in plasma of treatedpatients. This involved solid-phase extraction of 1 ml of plasmaonto carboxylic acid (CBA) grafted silica cartridges followed byreversed-phase liquid chromatography with UV detection. The bestselectivity was obtained through the use of C18 Uptisphere® asstationary phase. The low limit of quantitation obtained (LOQ:5 ng/ml) allowed measurements of docetaxel up to 24 hours afterone-hour infusions with low dosages of drug (60 mg/m2). Themethod was applied successfully to monitor docetaxel plasma levelswithin two protocols associating fixed dosages of either methotrexate or gemcitabine with escalating doses of Taxotere®.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006327302041
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  • 94
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    Application of a Combined “Effect Compartment/Indirect Response Model” to the Central Nervous System Effects of Tiagabine in the Rat (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 301-323 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacodynamics ; effect compartment model ; indirect response ; sigmoid E max ; tiagabine ; GABA uptake inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacological inhibition of GABA uptake transporters provides a mechanism for increasing GABAergic transmission, which may be useful in the treatment of various neurological disorders. The purpose of our investigations was to develop an integrated pharmacokinetic–pharmacodynamic (PK/PD) model for the characterization of the pharmacological effect of tiagabine, R-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl)nipecotic acid, in individual rats in vivo. The tiagabine-induced increase in the amplitude of the EEG 11.5–30 Hz frequency band (β), was used as pharmacodynamic endpoint. Chronically instrumented male Wistar rats were randomly allocated to four groups which received an infusion of 3, 10, or 30 mg kg −1 $$(\bar x \pm SE,{\text{ }}n = 23)$$ $$96 \pm 9$$ ml min -1 kg−1, 1.5ŷ0.1 L kg−1 and 20ŷ0.2 min.A time delay was observed between the occurrence of maximum plasma drug concentrations and maximal response. A physiological PK/PD model has been used to account for this time delay, in which a biophase was postulated to account for tiagabine available to the GABA uptake carriers in the synaptic cleft and the increase in EEG effect was considered an indirect response due to inhibition of GABA uptake carriers. The population values for the pharmacodynamic parameters characterizing the delay in pharmacological response relative to plasma concentrations were keo=0.030 min −1 and kout=81 min−1, respectively. Because of the large difference in these values the PK/PD model was simplified to the effect compartment model. Population estimates $$(\bar x \pm SE)$$ were E0=155 ŷ 6 μV, Emax=100 ŷ 5 μV, EC50=287 ŷ 7 ng ml−1, Hill factor=1.8 ŷ 0.2 and keo=0.030 ŷ 0.002 min −1. The results of this analysis show that for tiagabine the combined “effect compartment-indirect response” model can be simplified to the classical “effect compartment” model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020999114109
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  • 95
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    Assuming Peripheral Elimination: Its Impact on the Estimation of Pharmacokinetic Parameters of Muscle Relaxants (1999)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 491-512 
    Details
    ISSN: 1573-8744
    Keywords: muscle relaxants ; peripheral elimination ; pharmacokinetics ; peripheral concentrations ; volume of distribution ; pharmacokinetic model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract For anesthetic drugs undergoing nonorgan-based elimination, there is a definite trend towards using pharmacokinetic (PK) models in which elimination can occur from both central (k10 ) and peripheral compartments(k20 ). As the latter cannot be assessed directly, assumptions have to be made regarding its value. The primary purpose of this paper is to evaluate the impact of assuming various degrees of peripheral elimination on the estimation of PK parameters. For doing so, an explanatory model is presented where previously published data from our laboratory on three muscle relaxants, i.e., atracurium, doxacurium, and mivacurium, are used for simulations. The mathematical aspects for this explanatory model as well as for two specific applications are detailed. Our simulations show that muscle relaxants having a short elimination half-life are more affected by the presence of peripheral elimination as their distribution phase occupies the major proportion of their total area under the curve. Changes in the exit site dependent PK parameters (Vdss ) are also mostly significant when k20 is smaller than k10 . Although the physiological processes that determine drug distribution and those affecting peripheral elimination are independent, the two are mathematically tied together in the two-compartment model with both central and peripheral elimination. It follows that, as greater importance is given to k20 , the rate of transfer from the central compartment (k12 ) increases. However, as a result of a proportional increase in the volume of the peripheral compartment, peripheral concentrations remain unchanged whether or not peripheral elimination is assumed. These findings point out the limitations of compartmental analysis when peripheral elimination cannot be measured directly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1023286329945
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  • 96
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    Interspecies Scaling of Bosentan, A New Endothelin Receptor Antagonist and Integration of in Vitro Data into Allometric Scaling (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 97-101 
    Details
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics ; clearance ; in vitro models ; bosentan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The goal of this study was to find a rational and reliable method of using animal data to predict the clearance of metabolised drugs in humans. Methods. One such approach is to use in vitro liver models (e.g. hepatocytes and microsomes) to determine the relative capacities of the various animal species and humans to metabolise the test compound. These data can then be combined with the in vivo clearances in animals, to calculate the in vivo clearance in humans using allometric scaling techniques. In this study, this approach was evaluated with a new endothelin receptor antagonist, bosentan, which is eliminated mainly through metabolism and is characterized by very large interspecies differences in clearance. Therefore, this compound provided a stringent test of our new extrapolation method for allometric scaling. Results. The results obtained with bosentan showed that adjusting the in vivo clearance in the different animal species for the relative rates of metabolism in vitro gave a far better prediction of human clearance than an empirical correcting factor (brain weight). Conclusions. This approach provided a more rational basis for predicting the clearance of metabolised compounds in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016037519116
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  • 97
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    Percutaneous Absorption of Ketoprofen from Different Anatomical Sites in Man (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 168-172 
    Details
    ISSN: 1573-904X
    Keywords: ketoprofen ; nonsteroidal anti-inflammatory agent ; topical application ; percutaneous absorption ; regional variation ; pharmacokinetics ; urinary excretion ; enantiomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to investigate the percutaneous absorption of ketoprofen applied topically to different anatomical sites on the body. Methods. The study design was a randomized, four-way crossover in 24 healthy male subjects. One gram of ketoprofen 3% gel (30 mg dose) was applied every six hours for 25 doses over a 100 cm2 of the back, arm, and knee. A 0.5 ml of ketoprofen solution (60 mg/ml) was applied to the back as a reference treatment. Plasma and urine samples were obtained for the assay of racemic ketoprofen and ketoprofen enantiomers (S and R), respectively. Results. The relative bioavailabilities of ketoprofen gel were 0.90 ± 0.50, 1.08 ± 0.63, and 0.74 ± 0.38 when applied to the back, arm, and knee, respectively. The plasma ketoprofen Cmax for gel applied to the back and arm were similar (p 〉 0.05) but Cmax was lower when applied to the knee (p 〈 0.05). The time to Cmax ranged from 2.7 to 4.0 hours and was similar for gel treatments on the back and arm, but longer for the knee treatment. The fraction of dose excreted in urine as total S and R enantiomers ranged from 5.41 to 9.10%. Conclusions. The percutaneous absorption of ketoprofen was similar when applied to either the back or arm but was lower when applied to the knee.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016014308638
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  • 98
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    Pharmacokinetics of eltanolone following bolus injection and constant rate infusion (1996)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 24 (1996), S. 535-549 
    Details
    ISSN: 1573-8744
    Keywords: eltanolone ; pregnanolone ; Kabi 2213 ; context sensitive time ; anaesthesia ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disposition of intravenous anaesthetic eltanolone was studied when administered as a bolus injection (B) of 0.75 mg/kg and constant rate intravenous infusion at 2 mg/kg/hr (I2) and 3.5 mg/kg/hr (I3.5) for 2 hr in healthy male volunteers. Venous blood samples were collected for 12 hr and 20 hr following bolus injection and intravenous infusion, respectively. Serum eltanolone concentrations were determined by a specific gas chromatographic mass spectrometric assay. Using a nonlinear regression analysis, the individual data sets were best fitted by a three-compartment mamillary model with central elimination. Derived pharmacokinetic parameters expressed as median and 95% confidence intervals indicated an initial fast distribution with a half-life of 1.80 (0.23–5.47) min (B), 1.44 (0.97–2.06) min (I2) and 1.44 (0.95–2.39) min (I3.5), an intermediate phase with a half-life of 35.4 (28.7–45.2) min (B), 39.6 (31.0–47.9) min (I2) and 35.4 (33.3–44.9) min (I3.5) and a moderately short terminal phase with a half-life of 3.8 (2.7–5.9) hr (B), 5.0 (4.2–6.1) hr (I2) and 4.6 (4.0–4.8) hr (I3.5). The serum clearance after bolus injection was 1.37 (1.23–1.67) L/hr/kg and after infusion was 1.36 (1.25–1.52) L/hr/kg (I2) and 1.17 (1.11–1.31) L/hr/kg (I3.5). The pharmacokinetics of eltanolone appear to be linear over the dosage range studied. Pharmacokinetic parameters obtained after bolus injection were very much similar to the parameters obtained after infusion with the exception of t1/2β which was longer after the infusion (significant) and the volume of central compartment which was lower after infusion (not significant). Context sensitive times were estimated for a 30%, 50% and 80% drop in the concentration of eltanolone after different infusion times. A 30% drop in concentration is estimated to take about 2 to 3 min. A 50% drop in concentration, is estimated to take about 8 min when duration of infusion is 3 hr and reaches a value of about 10 min by a duration of infusion of 10 hr. A 80% drop in concentration is estimated to take about 55 min following an infusion of 1 hr and it reaches a value of 70–80 min following an infusion of 10 hr.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02353479
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  • 99
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    Bioequivalence assessment of etoposide phosphate and etoposide using pharmacodynamic and traditional pharmacokinetic parameters (1996)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 24 (1996), S. 313-325 
    Details
    ISSN: 1573-8744
    Keywords: etoposide ; etoposide phosphate ; bioequivalence ; pharmacokinetics ; pharmacodynamics ; humans ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioequivalence of etoposide phosphate, a prodrug of etoposide, to etoposide was assessed in a randomized, crossover study in 29 patients with histologically established solid tumors that had failed conventional treatment. Cohorts of patients received one treatment course each of etoposide and etoposide phosphate which consisted of a 100 mg/m2 per day etoposide equivalent dose infused iv over 1 hr on a Day 1 to 5 schedule of treatment. The second course was administered 21 days later or on recovery of blood cell counts. Plasma and urine samples were collected over 24 hr on Day 1 of each course and assayed for etoposide content by a validated HPLC/UV method. Resulting data were subjected to noncompartmental pharmacokinetic analysis. Hematology profiles were obtained by collecting blood samples prior to the first course and twice a week after each course. The pharmacodynamics and pharmacokinetics of etoposide were virtually identical after the two treatments. The point estimates (90% confidence intervals) for nadir WBC, granulocytes, hemoglobin, and platelets expressed as % decrease from the baseline, and for the pharmacokinetic parameters, Cmax, and AUC0-∞, after intravenous etoposide phosphate relative to etoposide were 100% (96%, 105%), 97% (91%, 103%), 95% (82%, 109%), 95% (84%, 106%), 107% (101%, 113%), and 113% (107%, 119%), respectively. Therefore, etoposide phosphate is bioequivalent to etoposide based on pharmacokinetic and pharmacodynamic assessments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02353515
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  • 100
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    Electronic Resource
    In vivo relationships between the cerebral pharmacokinetics and pharmacodynamics of thiopentone in sheep after short-term administration (1996)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 24 (1996), S. 1-18 
    Details
    ISSN: 1573-8744
    Keywords: thiopentone ; pharmacokinetics ; pharmacodynamics ; brain ; cerebral blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The cerebral kinetics and dynamics of thiopentone after infusions of 250, 500, and 750 mg over 2 min were examined in chronically instrumented sheep (6, 6, and 5 sheep per dose, respectively). The cerebral kinetics were studied by rapid sampling of arterial and dorsal sagittal sinus blood (afferent and efferent blood for the brain, respectively) for 40 min, and could be described by a single flow-limited compartment when arterial concentrations and cerebral blood flow were used as forcing input functions. The half-lives of equilibration between blood and the brain were estimated to be 0.67 (SEM=0.07), 0.57 (0.03) and 0.74 (0.05) min for the 250-, 500- and 750-mg doses, respectively, showing that the cerebral concentrations of thiopentone rapidly equilibrate with the afferent blood concentration. Simultaneous pharmacodynamic measurements included cerebral blood flow via a Doppler flowmeter on the sagittal sinus, and an index of the depth of anesthesia based on an algesimetry method. Thiopentone transiently reduced cerebral blood flow to 82 (SEM=3), 80% (7), and 74% (10) of baseline for the 250−, 500−, and 750-mg doses, respectively, and failure to account for drug-induced changes in cerebral bloof flow in the model overestimated the apparent volume of the brain by 12% for the 500-mg dose. For the 500-mg dose, the changes in cerebral blood flow could be accounted for by an effect compartment with a half-life of 0.82 min for arterial blood, and 0.00 min for sagittal sinus blood, showing the effluent brain concentrations were in equilibrium with this drug effect. The time course of the depth of anesthesia for the 250-mg dose could be accounted for by an effect compartment with a half-life of 1.33 min for arterial blood, and 0.41 min for sagittal sinus blood. Thus, the rate of equilibration between blood and brain could not account for all of this delay. It is concluded that after short-term administration thiopentone equilibrated rapidly with the brain, and that this is consistent with the observation that the magnitude of its clinically relevant effects closely follow the time course of the arterial blood concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02353508
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