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  • man  (57)
  • oxidation  (57)
  • Springer  (114)
  • American Chemical Society
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Wien : Geolog. Bundesanst.
  • 2010-2014
  • 1975-1979  (114)
Collection
Keywords
Publisher
  • Springer  (114)
  • American Chemical Society
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Wien : Geolog. Bundesanst.
Years
Year
  • 1
    Electronic Resource
    Electronic Resource
    Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 395-399 
    Details
    ISSN: 1432-1041
    Keywords: cyproheptadine ; metergoline ; glucose tolerance ; insulin secretion ; chemical diabetes ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561737
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of quinidine related to plasma protein binding in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 187-192 
    Details
    ISSN: 1432-1041
    Keywords: quinidine ; plasma protein binding ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134–0.303 (mean 0.221). Elimination rate constant (β) varied from 0.071 to 0.146 h−1 (mean 0.113), and apparent volume of distribution (Vβ) varied from 1.39–3.20 l · kg−1β (mean 2.27). Total body clearance was 2.32–6.49 ml min−1 · kg−1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both Vβ (r=0.885, p〈0.01) and total body clearance (r=0.668, p〈0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compund and its elimination rate will remain unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563104
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  • 3
    Electronic Resource
    Electronic Resource
    Use of a simulation model to study the acute haemodynamic effects of diazoxide in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 73-81 
    Details
    ISSN: 1432-1041
    Keywords: simulation model ; diazoxide hypotension ; haemodynamics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute haemodynamic effects of injected diazoxide (Hyperstat® Schering) have been studied in 8 hypertensive subjects. Aortic blood pressure was measured and cardiac output and peripheral conductance were assessed continuously using a simulation model. In six of the patients pulmonary artery end-diastolic pressure was also measured. Blood pressure fell in all subjects 5–10 min after injection of the drug cardiac output increased in all patients studied. However, the initial change in cardiac output differed, as it decreased in two subjects and did not change in one. The largest initial increases in cardiac output were seen in the subjects with the highest pulmonary artery end-diastolic pressure. Patients with an initial decrease in cardiac output were those with the least compliant (stiffest) aortas. We consider that the responsiveness of the baroreceptors determines the size of the increase in cardiac output immediately after reduction of blood pressure by diazoxide. Thus in a patient with a stiff aorta, particularly at low cardiac filling pressure, diazoxide might cause a fall in blood pressure to an unacceptable level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609868
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  • 4
    Electronic Resource
    Electronic Resource
    High-temperature oxidation of copper-manganese alloys (1979)
    Springer
    Oxidation of metals 13 (1979), S. 181-195 
    Details
    ISSN: 1573-4889
    Keywords: copper-manganese alloys ; oxidation ; scale composition
    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 copper-manganese alloys (2–35 wt. % Mn) in pure oxygen at 760 Torr was investigated at 100° intervals between 550 and 850°C. Gravimetric measurements of the oxidation kinetics have been combined with microstructural studies of the reacted samples in order to evaluate the reaction mechanisms. The scales formed on Cu-2Mn, Cu-5Mn, Cu-10Mn are always composed of three different layers; in any case manganese is present only in the inner layer. The scales formed on Cu-20Mn and Cu-35Mn are composed of two layers, both containing manganese, with a more Cu-rich outer layer. In all the samples internal oxidation in combination with external scale formation is observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00611978
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  • 5
    Electronic Resource
    Electronic Resource
    The oxidation of Fe-Cr surface and bulk alloys at 300°C (1979)
    Springer
    Oxidation of metals 13 (1979), S. 283-298 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; surface alloys ; Fe-Cr alloys ; iron ; kinetics
    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 several surface and bulk Fe-Cr alloys and iron at 300°C and 4×10−6 Torr oxygen was studied. The surface alloys were fabricated by implantation of 25 keV Cr ions into the outermost 300Å of polycrystalline iron samples. The oxide thickness as a function of oxygen exposure was obtained using proton-excited X-ray analysis, and composition profiles of oxide films were obtained using Auger electron spectroscopy and ion sputtering. The addition of Cr to Fe by surface and bulk alloying caused the oxidation rate to decrease and changed the oxidation kinetics from parabolic (for Fe) to logarithmic (for Cr concentrations ≥4.7at.%). Interpretation of the data in terms of simple oxidation theories indicates that the Cr additions may reduce the oxidation rate by altering the electronic properties of the metal-oxide interface.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00603672
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  • 6
    Electronic Resource
    Electronic Resource
    Oxidation of iron-nickel aluminum alloys in oxygen at 600–800° C (1979)
    Springer
    Oxidation of metals 13 (1979), S. 311-330 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; oxide maps ; alloying additives ; Fe-Ni-Al 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 oxidation behavior of iron-nickel-aluminum alloys containing 0–40 wt.% nickel and 0–30 wt.% aluminum has been investigated at 600 and 800° C. Through the construction of “oxide maps” it can be shown that three possible oxide morphologies may exist: Alloys containing less than approximately 5 wt.% aluminum form scales consisting of predominantly Fe2O3 and spinel; alloys with between 5 and 10 wt.% aluminum form Al2O3 scales interspersed by Fe2O3 nodules, and alloys with greater than 10 wt.% aluminum form predominantly γ-Al2O3 scales.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609303
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  • 7
    Electronic Resource
    Electronic Resource
    Surface oxidation of nickel metal as studied by X-Ray photoelectron spectroscopy (1979)
    Springer
    Oxidation of metals 13 (1979), S. 223-236 
    Details
    ISSN: 1573-4889
    Keywords: nickel ; oxidation ; surface reactions ; X-ray photoelectron spectroscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract X-ray photoelectron spectroscopy has been used to study the oxidation of polycrystalline nickel metal. The results indicate that the oxidation process takes place in three stages; associative adsorption of molecular oxygen, followed by the combination of oxygen atoms with surface nickel atoms and, ultimately, the formation of bulk oxide. At room temperature only the first two stages can be detected. For exposures below 1 L the O 1s photoelectron spectrum is considered to be characteristic of an associatively adsorbed oxygen species, but for exposures above this value evidence for the formation of a monolayer of “NiO” is suggested by the development of an O 1s peak at 529.9 eV. Incorporation of oxygen into the nickel lattice is observed at temperatures 〉500°K. The activation energy for this place-exchange process was estimated at 1.80±0.06 eV.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00603667
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  • 8
    Electronic Resource
    Electronic Resource
    Oxidation of Fe-C alloys at 700°C (1979)
    Springer
    Oxidation of metals 13 (1979), S. 255-272 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; Fe-C ; graphite deposition ; nonadherent oxide ; kinetics
    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 of Fe-C alloys containing 0.5 and 1.0% C was studied in 1 atm O2 at 700° C. The oxidation rate is considerably slower than for pure Fe. The oxide scale formed is detached, multilayered, and overoxidized, containing little or no FeO. A thin film of graphite was identified at the metal-oxide interface by electron diffraction. It is proposed that the slow oxidation and abnormal scale are caused by a residue of graphite left at the metal surface from the oxidation of Fe3C. This inhibition of the oxidation of Fe by carbon at 700°C is in contrast to the stimulation observed at 500°C.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00603670
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  • 9
    Electronic Resource
    Electronic Resource
    Transport processes in the oxidation of Ni studied using tracers in growing NiO scales (1979)
    Springer
    Oxidation of metals 13 (1979), S. 519-543 
    Details
    ISSN: 1573-4889
    Keywords: nickel ; oxidation ; transport ; tracer ; duplex scale
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Experimental techniques have been developed for determining Ni63 and O18 tracer distributions in NiO scales ranging in thickness from ∼0.1 to 100 μ. These have been used to investigate Ni and O transport in scales on {100} Ni crystals and polycrystalline Ni in the temperature range 500–1300° C. NiO grown on {100} Ni crystals at 1000°C was uniform and compact and grew by the bulk diffusion of Ni in NiO by a vacancy mechanism. At temperatures below 800°C the principal transport mechanism was short-circuit diffusion of Ni in NiO. At all temperatures short-circuit diffusion of oxygen contributed to scale growth on polycrystalline Ni and was responsible for growth of the inner layer of duplex scales. The oxygen diffusion paths are believed to be micro-cracks induced by growth stresses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00812776
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  • 10
    Electronic Resource
    Electronic Resource
    The effect of cerium on the oxidation of Ni-50Cr alloys (1979)
    Springer
    Oxidation of metals 13 (1979), S. 159-180 
    Details
    ISSN: 1573-4889
    Keywords: nickel-chromium alloys ; oxidation ; high temperature ; cerium
    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 Ni-50Cr alloys with minor cerium additions was studied between 800 and 1100° Cin oxygen, air, and oxygen at reduced partial pressures. Optical and scanning electron metallography, X-ray diffraction, and electron-probe microanalysis techniques were used to characterize the changes in scale and substrate morphology and to identify the oxidation products. Platinum markers were used to determine the direction of ionic transport. The effects of cold work, initial alloy phase distribution, and cyclic oxidation were also studied. The Cr 2 O 3 scales on the cerium-containing alloys grew while being largely separated from the metal substrate. Oxidation rate, oxide grain growth, and the tendency of scales to spall on cooling were reduced substantially with increasing alloy cerium content. The first two effects are suggested to result from the interaction of cerium ions and cerium oxide particles with oxide grain boundaries in reducing grain-boundary diffusion and oxide-boundary mobility. The third is suggested to result from the thinner, finer-grained scales formed on the Ce-containing alloys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00611977
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  • 11
    Electronic Resource
    Electronic Resource
    Low-temperature oxidation of Fe-24 wt.%Cr (1979)
    Springer
    Oxidation of metals 13 (1979), S. 437-456 
    Details
    ISSN: 1573-4889
    Keywords: Fe-Cr ; oxidation ; kinetics ; oxide morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Ferritic polycrystalline Fe-24 wt.% Cr was oxidized in pure oxygen at 190 ≤ T≤490° C and pressures in the range 5.3×10−2–13.3 Pa for periods of up to 5 hr. The reaction proceeded in three stages. An initial period of accelerating rate was accompanied by oxide island nucleation and growth. Following island coalescence the rate was approximately logarithmic at low temperatures and somewhat slower than parabolic at high temperatures. Rate control during this period was thought to be due to mass transport through the oxide grain boundaries left by the island impingement process. During these first two stages the oxide formed was γ-M2O3 with possibly some spinel. The final stage of reaction involved the appearance of α-M2O3 on the outer oxide surface and a substantial slowing of the oxidation rate due to the low diffusivity in this phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605109
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  • 12
    Electronic Resource
    Electronic Resource
    Oxidation of high-chromium Ni-Cr alloys (1979)
    Springer
    Oxidation of metals 13 (1979), S. 119-158 
    Details
    ISSN: 1573-4889
    Keywords: nickel-chromium alloys ; oxidation ; high temperature ; kinetics ; mechanisms
    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 of binary Ni-Cr alloys containing 44 and 50 wt. % Cr has been studied over a range of oxygen partial pressures at temperatures between 800 and 1100°C. The effects of cold work, surface preparation, and distribution of the Cr-rich second phase have been studied. The oxidation behavior is complex and cannot be described by a single model. The oxide grows by short-circuit diffusion as well as bulk transport through Cr 2 O 3 scales. The scale-growth mechanism includes extensive metal-oxide separation requiring Cr vapor transport to the scale, compressive stresses within the oxide which result in scale bulging and cracking, and the formation of a second oxide layer which results in voids being incorporated into the scale. Any factor which reduces the oxide grain size, such as cold work, finer distribution of the Cr-rich α phase or reduced oxygen pressure, results in an increased oxidation rate of binary alloys because of an increased number of grain-boundary short-circuit diffusion paths.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00611976
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  • 13
    Electronic Resource
    Electronic Resource
    The oxidation of copper studied by electron scattering techniques (1979)
    Springer
    Oxidation of metals 13 (1979), S. 331-351 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; copper ; thin films ; electron microscopy ; electron diffraction
    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 of thin single-crystal (100) and (111) films of copper at pressures of around 10−5 Torr and temperatures of 400 to 700°C has been observed by medium-energy electron diffraction, scanning electron microscopy, scanning and conventional microscopy using diffracted electron beams in the reflection mode, transmission electron microscopy, and transmission electron diffraction. Epitaxed nuclei of oxide are observed to grow into very thin single-crystal plates, using oxygen previously trapped in the copper film. There is considerable diffusion of the copper film. There is considerable diffusion of the copper away from the oxide. Between the oxide crystallites the copper surfaces appear to be unoxidized. A mottled contrast of the diffracted beam images of the copper surface is shown to result from many-beam dynamical diffraction effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609304
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  • 14
    Electronic Resource
    Electronic Resource
    Improvements in oxidation resistance by dispersed oxide addition: Al2O3-forming alloys (1979)
    Springer
    Oxidation of metals 13 (1979), S. 381-401 
    Details
    ISSN: 1573-4889
    Keywords: Co-Cr-Al ; oxidation ; dispersed oxides ; oxide scale adherence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The improvement in oxidation resistance produced by small additions of active elements to Al 2O3-forming CoCrAl alloys is primarily dependent on the formation of oxide pegs which grow into the alloy around the internal oxide particles of the active element; void formation at the alloy-scale interface is also suppressed. The distribution of these pegs is critical and this paper demonstrates that an internal oxidation pretreatment can be used to convert the active element to its oxide in a controlled manner, thereby optimizing the peg distribution. Al2O3-forming CoCrAl containing 1% Hf or Ce is internally oxidized in a sealed quartz capsule containing a 50/50 powder mixture of CoAl-Al2O3; it was not possible to oxidize internally Y-containing alloys. The isothermal and cyclic oxidation resistance of these alloys is superior to that of alloys not given a prior treatment. Detailed metallographic examination indicates that the prior internal oxidation treatment produces a finer, more uniform distribution of oxide pegs penetrating into the alloy which is more efficient in combatting scale spallation. Furthermore, the lower residual hafnium content in the alloy minimizes large HfO2 precipitates and the formation of gross Al2O3 intrusions, which can initiate scale failure. Thus, by internally oxidizing the alloy first, the advantages of a high alloy Hf content (1%) in producing sufficient oxide pegs, but of the right size, coupled with minimal thickening of the surface scale, can be achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609306
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  • 15
    Electronic Resource
    Electronic Resource
    Reduction of absorption of digoxin, phenytoin and aspirin by activated charcoal in man (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 213-218 
    Details
    ISSN: 1432-1041
    Keywords: Activated charcoal ; acute intoxication ; digoxin ; phenytoin ; aspirin ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The inhibitory effect of activated charcoal 50 g suspended in water on the absorption of digoxin, phenytoin and aspirin was studied in six healthy volunteers in a cross-over manner. The absorption of digoxin and phenytoin were almost completely prevented (about 98%) when activated charcoal was ingested immediately after the drug. The total absorption of aspirin was inhibited by 70%, with clear postponement of absorption and partial release of aspirin from the charcoal in the gut: The peak serum concentration of aspirin was reduced by 95% by charcoal. When activated charcoal was ingested 1 hour after the drugs the inhibition of absorption was considerably less. However, since the absorption of larger doses of the drugs is often slow, the administration of an adequate dose of activated charcoal will be of definite value in the treatment of acute intoxication, even if delayed for several hours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609985
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  • 16
    Electronic Resource
    Electronic Resource
    Compensation of dietary induced reduction of tetracycline absorption by simultaneous administration of EDTA (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 129-131 
    Details
    ISSN: 1432-1041
    Keywords: Tetracycline absorption ; EDTA ; milk ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of tetracycline in man under the influence of concomitantly administered EDTA, milk and a combination of EDTA and milk has been investigated. Urinary excretion of the drug was measured for 30 h. The inhibitory effect of milk could be counteracted by simultaneous ingestion of EDTA, which resulted in almost equivalent urinary excretion of tetracycline compared to experiments done in the fasting state. Administration of EDTA alone, in a neutral dosage form, did not significantly change absorption of the drug, which contradicted previous findings. The possible use of EDTA during tetracycline therapy is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607444
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  • 17
    Electronic Resource
    Electronic Resource
    Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 277-280 
    Details
    ISSN: 1432-1041
    Keywords: Doxycycline ; iron ; charcoal ; enteral cycling ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the intestinal interactions of doxycycline (DC) with Fe++ and charcoal, two groups of healthy volunteers were given either 200 mg or 100 mg DC in capsules at 2 p. m. and 9 p. m., and blood samples for fluorimetric assay of DC were collected for 24 h starting at 8.30 a. m. on the following morning. A 24-h-urine was also collected. The test was subsequently repeated at one-week intervals, when the volunteers also ingested either ferrous sulphate (80 mg Fe++) or charcoal (4.0 g) immediately after the zero-time sample of DC and at 3, 8 and 12 h. Charcoal completely adsorbed DC in vitro in an artificial small intestinal fluid. Ferrous sulphate or charcoal did not modify the serum level or urinary excretion of DC after the 200 mg+200 mg dose, but ferrous sulphate did reduce the 24-h urinary excretion of DC after the 100 mg+100 mg dose. The serum half-life and AUC of DC were reduced by ferrous sulphate given after the 100 mg+100 mg dose of DC. Charcoal did not modify any parameter, even after the 100 mg+100 mg dose of DC. The results do not support existence of important enteral cycling of DC. Although oral ferrous sulphate can lower the serum level and shorten the serum half-life of DC, the acute experiment suggested that a therapeutic serum level of DC can be maintained despite treatment with iron in the doses used in iron-deficiency, and charcoal in the doses used in diarrhoeic states, if the drugs are administered several hours apart.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00560462
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  • 18
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    Preliminary studies of the kinetics of citalopram in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 69-73 
    Details
    ISSN: 1432-1041
    Keywords: Citalopram ; pharmacokinetics ; man ; steady state levels ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1–21/2 days). Steady state levels in the range 120–340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2–3 was recorded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00560260
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  • 19
    Electronic Resource
    Electronic Resource
    Investigation into the species-specific deacylation of penta-acetyl-gitoxin (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 425-430 
    Details
    ISSN: 1432-1041
    Keywords: Penta-acetyl-gitoxin ; 16-acetyl-gitoxin ; gitoxin ; mass spectrometry ; species-specific deacylation ; man ; rabbit ; guinea-pig ; rat ; blood ; intestinal mucosa ; liver homogenate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penta-acetyl-gitoxin (PAG) shows species-specific deacylation to 16-acetyl-gitoxin (16-AG; I and III) or gitoxin (II and IV) by homogenates of liver and intestinal mucosa of man (I), rabbit (II), guinea-pig (III) and rat (IV), whereas it is degraded into tri- and tetra-acetates by homogenates of guinea-pig myocardium as well as by human blood and serum. The identity of the principal and chloroform-extractable metabolites in human urine after PAG administration with 16-AG has been demonstrated by mass spectrometry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00716384
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  • 20
    Electronic Resource
    Electronic Resource
    Haemodynamic and tolerance studies in man of a new, orally active, selectiveβ 1-adrenoceptor agonist H 80/62 (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 163-170 
    Details
    ISSN: 1432-1041
    Keywords: H 80/62 ; haemodynamic effects ; noninvasive techniques ; selectivity ; β1-adrenoceptor agonist ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The selective β1-adrenoceptor agonist H 80/62 was administered intravenously and orally to healthy subjects and its effects on systolic time intervals, arterial blood pressure and heart rate were studied. Side-effects were noted too, and continuous ECG-recordings were made in order to study its arrhythmogenic effect. After i.v. administration of H 80/62 20 µg/kg body weight there was shortening of total electromechanical systole, the pre-ejection period and of the left ventricular ejection time, systolic blood pressure tended to increase, and diastolic blood pressure and heart rate were essentially unchanged. When administered orally as a sustained-release preparation in doses between 20 and 40 mg the haemodynamic effects were qualitatively the same as after i.v. administration, but in some studies there was a slight increase in heart rate. During exercise the systolic blood pressure and heart rate were identical after H 80/62 and placebo. The effect of the drug was maximal immediately after cessation of the i.v. infusion and basal values were regained within 60 min. After oral administration of a sustained-release formulation the effect was maximal after one hour and persisted for at least five to seven hours. The drug was well tolerated on repeated administration. The incidence of ventricular extrasystoles was possibly increased in one subject out of eight (11 ventricular extrasystoles during 18 h). The results of this Phase I study of H 80/62 warrant further evaluation of the drug in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609978
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  • 21
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    Effect of delayed administration of activated charcoal on nortriptyline absorption (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 445-447 
    Details
    ISSN: 1432-1041
    Keywords: Activated charcoal ; tricyclic antidepressants ; nortriptyline ; poisoning ; antidote ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Activated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, ‘Medicoal’ was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charchoal may therefore be useful in the treatment of tricyclic antide-pressant poisoning even if a delay of several hours ensues before medical help is sought.
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    URL: http://dx.doi.org/10.1007/BF00716388
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    Serum and plasma concentrations of clindamycin following a single intramuscular injection of clindamycin phosphate in maintenance haemodialysis patients and normal subjects (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 435-439 
    Details
    ISSN: 1432-1041
    Keywords: Intramuscular Clindamycin Phosphate ; serum levels ; half-lives ; renal Failure ; haemodialysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum levels of clindamycin bioactivity and total clindamycin were studied after single intramuscular injections of 300 mg of clindamycin phosphate in a group of 6 normal subjects and a group of 6 maintenance haemodialysis patients. The patients were studied during a non-dialysis period and then again during haemodialysis. Peak levels tended to be higher and elimination half-lives shorter in the patients than in the normal subjects. Possible reasons for these differences are discussed. There was no evidence that haemodialysis per se influenced the pharmacokinetics of clindamycin phosphate. The proportion of unhydrolysed clindamycin phosphate tended to be higher in the renal failure patients and the reason for this is not apparent. Little, if any, dosage modification is necessary in severe renal failure although there is probably little point in exceeding a dose of 300 mg intramuscularly every 8 h even in severe infections in patients with severe renal failure. The higher peak levels in patients with advanced renal failure indicate the need for further studies with repeated doses.
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    URL: http://dx.doi.org/10.1007/BF00716386
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    Bioavailability of norethindrone in human subjects (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 35-39 
    Details
    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
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    URL: http://dx.doi.org/10.1007/BF00606680
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    Oxidation-sulfidation behavior of iron-chromium-nickel alloys (1978)
    Springer
    Oxidation of metals 12 (1978), S. 227-245 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; sulfidation ; iron-chromium-nickel alloy ; thermochemical diagram ; parabolic rate constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Oxidation-sulfidation studies of Fe-Cr-8Ni alloys with 4, 12, and 22 wt. % Cr were conducted at 750 and 875°C in multicomponent gas mixtures that contained CO, CO2, CH4, H2, and H2S. The reaction processes resulted in parabolic kinetics. A chromium concentration in the range 0–12 wt. % in the alloy had a negligible effect on the parabolic rate constant; however, the rate constant for the alloy with 22 wt. % Cr was significantly lower. For a given sulfur partial pressure, the oxygen partial pressures required for the formation of a continuous oxide layer in an Fe-22Cr-8Ni alloy were ∼102 to 103 times those calculated for Cr-Cr2O3 equilibrium at temperatures of 875 and 750° C, respectively.
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    URL: http://dx.doi.org/10.1007/BF00616098
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  • 25
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    Oxidation of a Ni-Cr-Al alloy at 850°C in air containing HCl gas (1978)
    Springer
    Oxidation of metals 12 (1978), S. 451-471 
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    ISSN: 1573-4889
    Keywords: HCl gas ; H2O vapor ; Ni-Cr-Al alloy ; oxidation ; hot corrosion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Moist air containing HCl gas caused the oxide formed on a Ni-Cr-Al alloy at 850°C to crack during the early stages of growth, and extensive blistering and spalling occurred on cooling. In dry air containing HCl gas no oxide cracking was observed at temperature although the oxide blistered and spalled on cooling. In dry or moist air free from HCl an adherent protective oxide formed which did not spall on cooling. The oxide cracking at temperature has been attributed to the production of hydrogen by reaction of Cr and Al in the alloy with water vapor and the removal of NiO as NiCl2 by reaction with HCl gas. Hydrogen produced by reaction of water vapor or HCl with Cr or Al dissolved in the alloy at temperature, but on cooling the hydrogen was released, causing the oxide to blister and spall. Preoxidation of the alloy in HCl-free atmospheres eliminated these effects of HCl gas in short-term isothermal tests.
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    URL: http://dx.doi.org/10.1007/BF00612090
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  • 26
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    A microstructural study of the influence of NaCl vapor on the oxidation of a Ni-Cr-Al alloy at 850°C (1978)
    Springer
    Oxidation of metals 12 (1978), S. 1-22 
    Details
    ISSN: 1573-4889
    Keywords: NaCl vapor ; Ni-Cr-Al alloy ; oxidation ; hot-salt corrosion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract A thin protective oxide formed on a Ni-19.7 Cr-2.4 Al alloy in air at 850°C. Microstructural examination of stripped films showed that the oxide was duplex with an inner chromium-rich layer of NiCr2O4 + Cr2O3 with probably some NiAl2O4 + Al2O3, and an outer nickel-rich layer, principally NiO. The oxide grew faster in the presence of NaCl and it differed significantly in microstructure and composition from a very early stage. The thicker regions of the oxide assumed regular polyhedral shapes in air + NaCl, rather than the irregular nodular shape exhibited in clean air, as well as becoming richer in chromium. The results suggest that chloride vapor increases cationic mobility in the oxide. It is proposed that Cl− ions are incorporated in the oxygen close-packed lattice, thereby increasing ionic mobility in Cr2O3.
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    URL: http://dx.doi.org/10.1007/BF00609972
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    A new approach to the study of the oxidation of metals in hostile environments (1978)
    Springer
    Oxidation of metals 12 (1978), S. 83-110 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; iron ; chromium ; Fe-9% Cr alloy ; Auger electron spectroscopy
    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 or general corrosion behavior of metals at pressures of 1 atm or more is usually investigated by oxidizing samples under prescribed conditions and then subsequently characterizing the surface produced using one or more of the experimental methods available. This article describes a method which obviates the necessity of transferring samples from the oxidizing environment to the instrument for analysis, is nondestructive, and monitors the oxidizing surface in situ. The oxidation of iron, chromium, and a 9% chromium-iron alloy in carbon dioxide at atmospheric pressure and at 773°K is described. The surfaces of these materials were analyzed by Auger electron spectroscopy during exposure to the gas. Spectra and diagrams illustrating the variation in surface composition as oxidation proceeded are shown and possible mechanisms for the oxidation reactions are briefly discussed. The formation of the surface oxide on iron and on the 9% Cr-Fe alloy appears to follow very similar paths under the conditions of oxidation used. In all the materials studied trace impurities such as sulfur participated in the oxidation reactions.
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  • 28
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    High-temperature oxidation kinetics of Cu-Si alloys containing up to 4.75 wt.% Si in $$p_{{\text{O}}_{\text{2}} } $$ =0.01 atm and pure CO2 (1978)
    Springer
    Oxidation of metals 12 (1978), S. 323-329 
    Details
    ISSN: 1573-4889
    Keywords: Cu-Si alloys ; oxidation ; kinetics ; silica
    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 of Cu-Si alloys (containing up to 4.75 wt. % Si) in $${\text{p}}_{O_2 } $$ =0.01 atm from 800 to 1000°C has been investigated using thermogravimetry and other techniques. A 0.04% Si alloy followed a parabolic oxidation law with a rate similar to that of pure Cu. As the Si concentration increased the rate decreased and became irregular owing to SiO2 particles or flakes at the alloy-scale interface. It is considered that sintering of SiO2 particles and rupture of the sinter because of contraction during sintering are responsible for the irregular kinetics. A SiO2 layer forms directly on the 4.75% Si alloy which oxidizes uniformly. The SiO2 was always amorphous. In pure CO2 a similar pattern of amorphous SiO2 particles, flakes, and layers occurs.
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    Oxidation of an Fe—19 wt. % Ni alloy in CO2 at 700–1000°C (1978)
    Springer
    Oxidation of metals 12 (1978), S. 215-225 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; Fe-Ni alloys ; kinetics ; scale morphology ; EPMA
    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 of an Fe—19.34 wt. % Ni alloy in dry CO2 has been studied at 700—1000°C using thermogravimetry, metallography, and EPMA. Weight gains for oxygen consumption followed a linear-parabolic-linear sequence at all temperatures. During the initial linear stage the scale consisted mainly of magnetite and the activation energy of 133±25 kJ · mole−1 is considered to be due to dissociation of CO2 into CO and adsorbed oxygen on the outer magnetite surface. During the parabolic oxidation stage a continuous Ni-rich layer containing ∼ 70% Ni forms a barrier to the diffusion which has an activation energy of 192±79 kJ · mole−1. The breakdown of the barrier layer causes a return to linear kinetics with an activation energy of 138±42 kJ · mole−1 for dissociation of CO2 on the outer surface. During the final linear stage there is pronounced general and intergranular subscale formation. Detailed information is presented of the Ni redistribution and concentrations during oxidation and its correlation with the kinetics and morphology.
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    URL: http://dx.doi.org/10.1007/BF00616097
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    The oxidation behavior of CoCrAI systems containing active element additions (1978)
    Springer
    Oxidation of metals 12 (1978), S. 35-66 
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    ISSN: 1573-4889
    Keywords: CoCrAl ; oxidation ; oxide scale adherence ; rare-earth effect ; hafnium ; yttrium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The effect of small amounts of yttrium (up to 1 wt. %) and hafnium (up to 1.5 wt.%) on the oxidation behavior of Co-Cr-Al alloys in the temperature range 1000–1200°C for times up to 1000 hr in air has been studied. The major portion of the study has been concerned with Co-10Cr-11Al base alloys. Both isothermal and cyclic tests have been carried out; the cycle used consisted of 20 hr at temperature, followed by cooling to room temperature. Both additions reduce the overall oxidation, Hf somewhat more so than Y. In part, this is due to the improved adhesion between scale and alloy reducing scale spallation at temperature, and in part due to possible modification of the Al2O3 grain size. The former factor is far more critical under thermal cycling conditions. Under isothermal conditions the oxidation rate increases with increasing Hf content with all but the 1.5 wt.% alloy oxidizing more slowly than the Hf-free alloy; increase in Y content has the reverse effect. Under thermal cycling conditions the 0.3 and 1.0 wt.% Hf alloys show the lowest overall weight gain. Metallographic evidence suggests that the improved scale adhesion is due principally to a pegging mechanism; the active elements promote the growth of intrusions of Al2O3 into the alloy. However, if the intrusions are too large, they can act as initiators of scale failure.
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    Application of the Rosenburg kinetic method for determination of the parabolic rate constants for metal oxidation (1978)
    Springer
    Oxidation of metals 12 (1978), S. 139-156 
    Details
    ISSN: 1573-4889
    Keywords: Rosenburg method ; oxidation ; CoO
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The Rosenburg continuous kinetic method is proposed for the determination of the parabolic rate constants of metal oxidation as a function of temperature and oxidant pressure. Using this method, it is possible to make numerous measurements in a continuous manner on a single metal sample left in situ in the furnace, thus eliminating systematic errors due to differences between samples. Moreover, using this method it is possible to determine directly from a given kinetic curve such important parameters as the coefficients of chemical diffusion and self-diffusion of the more mobile species in the studied compound and the total equilibrium defect concentration. The latter parameter has been inaccessible up to now by the experimental method. The limits of applicability of this method are given in the paper. As an example of this method, the kinetics of cobalt oxidation are investigated in the range of temperature 1000–1250°C and oxygen pressure 10−3−1 atm; the results compare favorably with those obtained by other authors. The method is, however, applicable to certain other systems, namely, metal oxides and sulfides.
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    URL: http://dx.doi.org/10.1007/BF00740256
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    The penetration by sulfur of NiO scales growing on nickel (1978)
    Springer
    Oxidation of metals 12 (1978), S. 173-181 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; hot corrosion ; sulfidation ; preoxidation ; scale penetration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The transport of sulfur through growing scales may occur by chemical (solution and diffusion) or physical (gas molecule permeation) mechanisms. Both possibilities are examined theoretically for the case of NiO growing on nickel. Experiments are designed and carried out to establish which mechanism plays the major role in sulfur transport. The results indicate that the physical mechanism is likely to be predominant.
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    Reaction of cobalt in Ar-SO2 atmospheres at 500–900°C (1978)
    Springer
    Oxidation of metals 12 (1978), S. 23-34 
    Details
    ISSN: 1573-4889
    Keywords: cobalt ; oxidation ; sulfidation ; conjoint attack
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The attack of cobalt by sulfur and oygen simultaneously in Ar-SO2 atmospheres in the temperature range 500–900°C has been found to conform to the pattern established by the attack of other metals under similar conditions. A thermodynamic and kinetic interpretation of the mechanism has been proposed. The results also indicate that during the initial stages sulfur diffuses through the initially formed oxide layer, eventually leading to formation of the commonly observed duplex sulfide and oxide scale.
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    Oxidation of Fe-C alloys at 500°C (1978)
    Springer
    Oxidation of metals 12 (1978), S. 67-82 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; Fe-C ; kinetics ; oxide grain size ; grain-boundary diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Fe-C alloys containing 0.1, 0.5, and 1.0% C were oxidized in 1 atm O2 at 500°C. Two specimen preparations were used: annealed followed by slow cooling to form coarse pearlite plus proeutectoid ferrite or cementite; and cold-worked by abrading after annealing. The cold-worked alloys oxidize more rapidly. Annealed pearlite oxidizes faster than annealed ferrite. The differences in oxidation rate are caused by differences in the Fe3O4 grain size, that is, by the number of oxide grain boundaries available to act as easy diffusion paths for the outward diffusion of Fe through the Fe3O4. The oxidation rate constant is 10 times larger for fine-grained poly crystalline oxide than for oxide in which the Fe3O4 is monocrystalline.
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    High-temperature corrosion of nickel in SO2 (1978)
    Springer
    Oxidation of metals 12 (1978), S. 503-526 
    Details
    ISSN: 1573-4889
    Keywords: nickel ; sulfur dioxide ; 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 reaction of nickel with SO2 has been studied in the temperature range 650–1100°C at SO2 pressures from 10 to 760 Torr. Reaction kinetics have been studied by thermogravimetry; the reacted specimens have been characterized by means of metallography, scanning electron microscopy, and electron microprobe analysis. The reaction involves oxidation and sulfidation except at sufficiently high temperatures and low pressures of SO2 (e.g., 1000°C and 10 Torr SO2) where only formation of NiO takes place. Approximately linear reaction kinetics are observed between 650 and 900°C. Reaction mechanisms are discussed, and the relative importance of oxide formation and sulfidation is interpreted in terms of the thermodynamics of the Ni-O-S system.
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    Thickness determination of oxide films on iron by electron back-scattering Mössbauer spectroscopy (1978)
    Springer
    Oxidation of metals 12 (1978), S. 247-256 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; iron ; magnetite ; oxide thickness ; electron back-scattering Mössbauer spectroscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Magnetite films in the range 265–4520 Å have been grown on natural iron substrates and subsequently investigated by electron back-scattering Mössbauer spectroscopy. In particular, the percentage, P, of the total spectrum area contributed by the oxide has been determined as a function of oxide thickness, d. It was found that d up to ≈ 3000Å may be expressed (to an accuracy of ∼ 5%) by d (Å)=−1.95 × 103 ln (1–0.01 P). The experimental data have been compared with the theoretical predictions of both Huffman and Bainbridge. Good agreement between experiment and Huffman's predictions of P is obtained using values of the electron attenuation coefficient, μ, of 1.10 × 104 cm2 g−1 for the 7.3 keV electrons and 1.73 × 104 cm2 g−1 for the 5.4 keV electrons. A good fit of our data to Bainbridge's expression requires a somewhat lower effective μ, value of 0.8 × 104 cm2 g−1. The experimental P value for the thickest oxide (4520 Å) is lower than the theoretical predictions, probably as a result of a neglected mechanism recently identified by Tricker, Ash, and Cranshaw.
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    High-temperature corrosion and creep of Ni-Cr-Fe alloys in carburizing and oxidizing environments (1978)
    Springer
    Oxidation of metals 12 (1978), S. 387-404 
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    ISSN: 1573-4889
    Keywords: carburization ; oxidation ; austenitic Fe-Ni-Cr alloys ; internal carbide formation ; high-temperature corrosion and creep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The carburization of NiCr 32 20 and NiCrSi 60 16 has been studied in CH4-H2 mixtures in the temperature range 900–1100°C. The methods included thermogravimetric measurements and studies on reacted specimens by X-ray diffraction, metallographic, and chemical analysis. Upon carburization internal carbides M7C3 and M23C6 are formed (M=mainly Cr); the rate of carburization is determined by carbon diffusion in the Fe-Ni matrix with carbide precipitations. The effect of the alloying elements Ni and Si on the carburization resistance of austenitic alloys is explained. By the same methods the oxidation and carburization in CO-H2O-H2 mixtures have been studied. The important role of a stable chromium oxide layer for the carburization resistance was confirmed. Creep tests at 1000°C in a CO-H2O-H2 atmosphere where Cr2O3 is stable showed carburization occurring through cracks in the oxide layer. At high strain rates premature failure occurs by carburization, which is followed by internal oxidation and formation of cracks, voids, and holes.
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    Effect of Ca++ and GABA on oxidation of glutamate and glutamine by rat brain synaptosomes (1978)
    Springer
    Bulletin of experimental biology and medicine 86 (1978), S. 1158-1160 
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    ISSN: 1573-8221
    Keywords: synaptosomes ; oxidation ; glutamine ; glutamate ; γ-aminobutyric acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Experiments in vitro showed that the addition of Ca++ inhibits respiration of rat brain synaptosomes in the presence of glutamate and glutamine. The addition of GABA potentiates the inhibitory effect of Ca++ on the oxidation of glutamine but not of glutamate. GABA itself has no effect on the oxidation of either glutamate or glutamine.
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    Plasma levels and half lives of thioridazine and some of its metabolites (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 141-147 
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    ISSN: 1432-1041
    Keywords: Phenothiazine ; thioridazine ; plasma level ; metabolic pattern ; half life ; man ; schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma-levels of thioridazine, mesoridazine, sulphoridazine and two other metabolites were determined in ten older chronic psychotic patients on thioridazine therapy. The plasma-level before the morning dose of thioridazine was the most reliable parameter for clinical studies. An intra-individual relationship between lower doses of thioridazine and plasma-levels was found. The percentage contribution of psychoactive compounds to the total sum of “thioridazine plus metabolites” ranged from 43–74%. The mean “early disappearance half-life” of thioridazine was 5 hours, and its mean “late disapperance half-life” was 26 hours.
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    The kinetics of ethanol absorption and elimination in twins and supplementary repetitive experiments in singleton subjects (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 337-344 
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    ISSN: 1432-1041
    Keywords: Twin study ; ethanol metabolism ; intra-individual variation ; pharmacogenetics ; plasma level ; man ; heritability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of genetic and environmental factors on the metabolism of a single oral dose of ethanol 1.2 ml per kg body weight was analysed in 19 identical and 21 fraternal healthy, adult, un-selected male twin pairs. The heritability values of the rates of absorption, degradation and elimination of ethanol were 0.57, 0.41 and 0.46 respectively. Environmental factors, such as daily alcohol intake and smoking, increased the rate of elimination of blood alcohol. Intrasubject variation in ethanol metabolism was studied by repeated tests in 11 male volunteers at intervals of at least 2 months, under the same conditions as in the twins; the coefficients of variation for parameters of metabolism was about 8%. The results demonstrate both genetic control of ethanol absorption, degradation and elimination and the appreciable influence of environmental factors. The almost total genetic control of ethanol metabolism postulated by Vesell et al. (1971) could not be confirmed.
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    Disposition and oxidative metabolism of phenylbutazone in man (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 359-366 
    Details
    ISSN: 1432-1041
    Keywords: Phenylbutazone ; 14C-label ; oxyphenbutazone ; gas chromatography ; disposition ; oxidative metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption and elimination of orally administered14C-phenylbutazone and the role of oxidation in its metabolism have been studied. The main routes of excretion of14C-phenylbutazone and its metabolites were investigated in 3 patients with rheumatoid arthritis, and in 1 patient with a T-tube in the common bile duct. Up to 9 days after an oral dose of14C-phenylbutazone 600 mg (30 µCi) 63% of the radioactivity was found in the urine and 14% had appeared in the faeces. The cumulative excretion of radioactivity in bile amounted to 9.5% of the dose in 4 days. Only 1% of the radioactivity in the urine and bile was due to unchanged phenylbutazone. The role of oxidative metabolism of phenylbutazone in healthy human subjects was studied by gas chromatography. In 3 subjects given a single dose of phenylbutazone 600 mg, only 8.3% of the dose was excreted in urine as oxidized metabolites after 5 days. However, in 5 patients who had taken phenylbutazone for more than 5 weeks, these metabolites accounted for 23.4% of the dose. These results suggest that oxidative metabolism becomes more important after continued administration of the drug. After a single dose of phenylbutazone, the side-chain oxidized metabolite (II) was the major free derivative excreted in urine, but the ring oxidized metabolite, oxyphenbutazone (I), was much more important than the former in plasma. However, after prolonged treatment there was little difference between the concentration of the two metabolites in plasma. This finding suggests that side-chain oxidation is increased relative to ring oxidation on prolonged treatment with phenylbutazone. A third derivative containing hydroxyl groups both in the phenyl ring and in the side-chain (metabolite III) was found in urine in experiments with phenylbutazone, but in only one out of 3 volunteers given repeated doses of oxyphenbutazone.
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    A sensitive radioimmunoassay for fentanyl (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 153-158 
    Details
    ISSN: 1432-1041
    Keywords: Fentanyl ; radioimmunoassay ; cross-reaction ; plasma level ; dog ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Antiserum to fentanyl was obtained in rabbits repeatedly injected with carboxyfentanyl conjugated to bovine serum albumin. Using the antiserum, a highly sensitive radioimmunoassay has been developed, based on the dextran-coated charcoal method. It proved possible to assay the drug directly in plasma, in amounts as small as 30 picogram in 0.5 ml. The antibody was highly specific for fentanyl and no cross-reaction was observed with its major metabolites. This sensitive and specific radioimmunoassay method was employed to determine fentanyl in plasma from six volunteers after an intravenous bolus of 0.2 mg, and in plasma from dogs treated both intravenously and subcutaneously with 0.02 mg/kg. The plasma level of fentanyl could be followed for up to 6 h after a therapeutic dose in dogs and man.
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    Plasma levels and half lives of thioridazine and some of its metabolites (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 135-140 
    Details
    ISSN: 1432-1041
    Keywords: Phenothiazine ; thioridazine ; metabolites ; plasma-level ; metabolic pattern ; half-life ; man ; schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of thioridazine and four of its metabolites were determined in a series of fifteen young acute schizophrenics. Consistent individually different metabolic patterns were detected in a group of patients who had the same value for the sum of thioridazine plus metabolites. The apparent volume of distribution and half life were calculated. Clinical evolution tended to correlate best with the level of mesoridazine.
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    Serum glycoside concentrations after single or repeated intravenous doses ofβ-methyl-digoxin and digoxin (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 213-218 
    Details
    ISSN: 1432-1041
    Keywords: β-Methyl-digoxin ; digoxin ; intravenous administration ; man ; serum concentration ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present investigation was to estimate the ratio of the intravenous doses ofβ-methyl-digoxin and digoxin required to produce identical serum glycoside concentrations in man. 20 patients on intravenous maintenance therapy were changed fromβ-methyl-digoxin to the identical dose of digoxin or vice versa. Each drug was given for 7 days. Serum concentrations 13% higher were found during administration ofβ-methyl-digoxin. Assuming a half life of 60 h after with drawal, the dose of digoxin producing the same minimum serum concentration was estimated to be 1.16 times higher than that ofβ-methyl-digoxin. 18 healthy volunteers received 0.4 mg β-methyldigoxin, and 23 the same dose of digoxin, as an intravenous infusion over 2 h. The serum concentrations and urinary glycoside excretion were measured over a period of 32 hrs. During the first hour after the infusion the serum concentration of digoxin declined more rapidly than that ofβ-methyl-digoxin. Thereafter, the ratio of the serum concentrations did not change appreciably up to the end of the investigation. The area under the serum concentration/time curve was about 13% greater forβ-methyl-digoxin than for digoxin; this difference was not significant. The average renal clearance was 96±9 ml forβ-methyl-digoxin, 151±13 ml for digoxin. Since the total body clearance of digoxin is only about 1.16 times higher than that ofβ-methyl-digoxin, the lower renal clearance ofβ-methyl-digoxin must partly be compensated by higher extrarenal clearance. From the ratios of the areas under the serum concentration/time curves after single doses of β-methyldigoxin and digoxin, and the minimum serum concentrations during maintenance therapy, it was concluded that the dose of digoxin to produce the same average serum concentrations would be about 1.15 times higher than that ofβ-methyl-digoxin. In comparison with the large variations in individual dosage of digoxin andβ-methyl-digoxin, this difference is too small to be of practical importance.
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    Smoking and catecholamine and c-AMP concentrations in the coronary circulation of man and the effect of oxprenolol (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 81-87 
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    ISSN: 1432-1041
    Keywords: Oxprenolol ; smoking ; catecholamines ; coronary circulation ; man ; c-AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Changes in catecholamine, c-AMP and lactate concentrations in the coronary circulation of man, during smoking, were studied in 12 patients. The heart rate increased from 63±2 beats/min (control) to 74±3 (smoking) (P〈0.01), falling to 70±2 (10 min after smoking) (0.05〉P〉0.01), whilst coronary sinus c-AMP concentrations rose from 11±0.7 nmol/l (smoking) to 11.9±0.8 nmol/l (after smoing) (0.05〉P〉0.01; one tailed ‘t’ test). There was no significant change in blood pressure, catecholamine or lactate concentrations. The study was repeated in eight of the patients following intravenous oxprenolol. Coronary sinus catecholamine concentrations increased from 4.1±0.7 nmol/l (control) to 5.5±1.1 nmol/l (after smoking) (0.05〉P〉0.01; one tailed ‘t’ test), but heart rate and c-AMP concentrations remained unchanged, confirming that smoking-induced tachycardia is a result of a β-adrenergic mechanism, at least part of which is due to a release of cardiac catecholamines. Arterial lactate concentrations increased only following oxprenolol from 0.74±0.07 mmol/l (control) to 0.83±0.09 mmol/l (smoking).
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    Influence of nutritional status on plasma levels and relative bioavailability of tetracycline (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 281-284 
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    ISSN: 1432-1041
    Keywords: Tetracycline ; bioavailability ; plasma levels ; nutritional state ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and undernourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in undernourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCl 250 mg at 6 hour intervals. However, in these studies undernourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.
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    The diffusional growth of a scale with variable composition, diffusivity, and molar volume (1977)
    Springer
    Oxidation of metals 11 (1977), S. 57-62 
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    ISSN: 1573-4889
    Keywords: oxidation ; scale growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Equations are presented to modify the classical theoretical expressions for the parabolic rate constant for the case in which the scale has a large composition range and a large variation in molar volume. The modifications appear as simple averages, together with a factor f.Evaluation of f for some hypothetical cases shows that it is near unity unless the composition gradient has an extreme deviation from linearity.
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    Thickness of the oxide layers formed during the oxidation of iron (1977)
    Springer
    Oxidation of metals 11 (1977), S. 193-198 
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    ISSN: 1573-4889
    Keywords: oxidation ; scaling ; wustite ; magnetite ; iron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The theory of the growth of two oxide layers by Yurek et al. has been applied to the oxidation of iron at 1100° C. The theoretical parabolic rate constants for the simultaneous growth of the two oxide layers were calculated from radioactive tracer diffusion coefficients for wustite and magnetite. Good agreement was found between the theoretical and experimental values of the ratio of scale thicknesses.
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    Behavior of oxide films on high-temperature alloys in carbonaceous gas atmospheres (1977)
    Springer
    Oxidation of metals 11 (1977), S. 23-56 
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    ISSN: 1573-4889
    Keywords: oxidation ; carburization ; carbonaceous gases ; superalloys ; stainless steels ; film formation ; structure of oxide scales ; preoxidation ; metal dusting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Formation and deterioration of oxide films on several contemporary high-temperature alloys was studied in various carbonaceous gas atmospheres. Scanning electron microscopy and metallographic examination were applied to films on Fe-Cr-Ni and Ni-Cr-Al type alloy compositions exposed in CH 4/H2 and CO/CO2 atmospheres at temperatures up to 900° C and pressures up to 900 psi (6.2 × 106 N/m2). The effects of various preoxidation treatments were evaluated. Reduction of certain oxide phases is observed to promote catalytic gas decomposition. Al2O3 components in the films are observed to be stable under the reducing conditions experienced. Carbon uptake by various alloys is found to be quite sensitive to surface finish, with an observed increase in penetration with surface roughness.
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    Oxidation of tantalum in oxygen-nitrogen and oxygen-inert gas mixtures (1977)
    Springer
    Oxidation of metals 11 (1977), S. 225-239 
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    ISSN: 1573-4889
    Keywords: tantalum ; oxidation ; high temperature ; kinetics
    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 of tantalum in oxygen-nitrogen and oxygen-inert gas mixtures at925°C has been studied. The oxygen pressure was close to 0.5 atm in all experiments, and partial pressures of the second component of from 0 to 180 Torr were employed. Spherical specimens were used to provide quantitatively significant kinetic data. A model has been proposed which suggests that the oxygen pressure at the reaction interface close to the metal surface is lower than the external pressure because of the finite permeability of the porous outer oxide layer, and that the inert gas effectively reduces the permeability. The model gives good quantitative agreement with the experimental results.
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    The effect of ΔT (oxidizing temperature minus cooling temperature) on oxide spallation (1977)
    Springer
    Oxidation of metals 11 (1977), S. 91-106 
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    ISSN: 1573-4889
    Keywords: oxidation ; cyclic ; spallation ; stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Several alloys (one iron base and five nickel base) were cyclically oxidized in a series of tests in which the higher temperature (1100 or 1200° C) of the cycle was fixed at a level to allow ample oxidation in reasonable time and the lower temperature was variable to allow cycle temperature differences (ΔT s ) of up to 1400°C. The alloys oxidized included those which formed simple oxides such as Al2O3 or Cr2O3, as well as those which formed complex scales. Cooling rates were relatively low to minimize thermal shock effects. Each cycle consisted of 1 hr at the higher temperature and 1/2 hr at the lower temperature. Samples were tested up to 370 cycles. The extent of attack was determined by specific weight change which was continuously monitored. For all nickel alloys, as ΔT increased the extent of spallation increased. This effect was attributed to thermal expansion mismatches between the oxide and the nickel substrate. The FeCrAl alloy was not sensitive to ΔTand resisted spalling at ΔT levels to 1400°C. FeCrAl, and the Al2O3 scale which forms on it, have thermal expansion coefficients which are substantially more alike than any of the other oxide-metal combinations tested.
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    The oxidation behavior of dilute Ni-V alloys at 1200°C (1977)
    Springer
    Oxidation of metals 11 (1977), S. 109-125 
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    ISSN: 1573-4889
    Keywords: nickel-vanadium ; 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 oxidation behavior of nickel and dilute Ni-V alloys has been studied in flowing oxygen at 1 atm pressure, using various kinetic and electron-optical techniques. The oxidation rate rises progressively as the alloy vanadium content is increased from 0 to 0.8% and then to 1.7%. However, further additions to 4.2% cause only a slight further increase. These increases in oxidation rate are largely controlled by the extent of doping of the NiO, particularly for the two more dilute alloys, although internal oxidation, spinel blocking effects in the oxide, and dissociation of the NiO affect the weight gains to some extent, particularly for the case of the Ni-4.2% V alloy.
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    The isothermal oxidation of Co-Cr alloys in 760 Torr oxygen at 1000°C (1977)
    Springer
    Oxidation of metals 11 (1977), S. 163-191 
    Details
    ISSN: 1573-4889
    Keywords: cobalt-chromium ; oxidation ; oxygen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The isothermal oxidation of Co-Cr alloys containing 0–30% Cr in 760 Torr oxygen at 1000° C has been studied kinetically and by appropriate physical techniques. Chromium additions to cobalt increase the parabolic oxidation rate to an almost constant level from 2 to 15% Cr, while further additions to 20–30% Cr decrease the rate. All the alloys produce a virtually pure CoO layer outside a layer containing Co-Cr spinel particles in a Cr3+ -doped CoO matrix. The variation of oxidation rate with alloy chromium content is explained in terms of the complex interplay of doping, blocking of cation transport by voids and spinel particles and short circuiting by transport of dissociative oxygen across these voids and other processes, internal oxidation making a negligible direct contribution to weight gain. Complete spinel layers are never quite developed under the conditions studied, although formation of spinel does slow the oxidation rate. The improved protection eventually obtained at higher chromium levels is produced by the tendency to form a Cr2O3 healing layer.
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    Volatilization of oxides during oxidation of some superalloys at 1200°C (1977)
    Springer
    Oxidation of metals 11 (1977), S. 289-305 
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    ISSN: 1573-4889
    Keywords: superalloys ; oxidation ; oxides ; volatilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Volatilization of oxides during cyclic oxidation of commercial Nichrome, Inconel 750, René 41, Stellite 6B, and GE-1541 was studied at 1200°C in static air. Quantitative analysis of oxide vapor deposits revealed that oxides of tungsten, molybdenum, niobium, manganese, and chromium volatilized preferentially from the oxide scales. Aluminum and silicon were not detected in vapor deposits. For all the alloys except GE-1541 chromium was found to be the main metallic element in the oxide scales.
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    Rheography of the stomach (1977)
    Springer
    Bulletin of experimental biology and medicine 84 (1977), S. 1060-1064 
    Details
    ISSN: 1573-8221
    Keywords: rheography ; stomach ; animals ; man ; sensitive probe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A practical method of rheography is suggested for studying the state of the human gastric circulation. The theoretical aspects of the use of a bipolar system of electrodes (external and internal) with essentially different sizes of contact surface are examined with respect to the stomach. A scheme and brief description of the simple apparatus are given. Control experiments were carried out on animals to confirm the validity of the basic assumptions. Mean values of some rheographic indices frequently used in clinical practice, based on rheograms of the stomach of 30 healthy subjects, are given.
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    Effect of the aldosterone antagonist canrenone on plasma aldosterone concentration and plasma renin activity, and on the excretion of aldosterone and electrolytes by man (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 253-257 
    Details
    ISSN: 1432-1041
    Keywords: Aldosterone ; renin ; aldosterone antagonist ; canrenone ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Canrenone was administered in doses of 2×82 mg and 2×164 mg per day over a period of 10 days to diabetic patients without cardiovascular, liver or kidney involvement. Aldosterone excretion and plasma aldosterone increased only slightly during both regimes. There was a clear-cut increase in aldosterone excretion only after discontinuation of carenone. Excretion of sodium potassium and fluid was not significantly changed either during or after treatment. The lack of effect of canrenone on the kidney was in contrast to the significant decrease in serum sodium and increase in serum potassium, and the significant, dose-dependent rise in plasma renin activity following canrenone administration. The increased plasma renin activity persisted for some days after discontinuation of canrenone. It is suggested that canrenone primarily exerted its effect in the distal part of the large intestine where ionic movements are most affected by aldosterone. The disproportionately slight increase in plasma aldosterone concentration and aldosterone excretion, in spite of the greatly elevated plasma renin activity and serum potassium level, is considered to be due to a direct inhibitory effect of canrenone on aldosterone production in the adrenals.
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    Pharmacokinetics of lofepramine in man: Relationship to inhibition of noradrenaline uptake (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 291-298 
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    ISSN: 1432-1041
    Keywords: Tricyclic antidepresent ; lofepramine ; single- and multiple-dose kinetics ; noradrenaline and 5-hydroxytryptamine uptake ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lofepramine, an imipramine analogue, have been studied by administering single oral doses to volunteers, determination of plasma levels of lofepramine and desmethylimipramine after ten days of oral administration to patients, and by relating plasma levels to the effect on uptake of noradrenaline by isolated rat irides and brain slices of plasma samples collected during treatment. The results indicate that lofepramine undergoes pronounced first pass elimination and that desmethylimipramine is a major metabolite of it. During steady-state conditions the plasma level of lofepramine fluctuates considerably between doses. A linear relation was found between inhibition of neuronal uptake of noradrenaline and the plasma concentration of desmethylimpramine. No effect was seen on the uptake of 5-hydroxytryptamine in brain slices incubated in patients' plasma which suggests that neither lofepramine nor its metabolites formedin vivo in man affect neuronal uptake of this amine. Lofepramine belongs to the group of tricyclic anti-depressants which preferentially inhibit noradrenaline uptake.
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    Absorption of β-methyl-digoxin determined after a single dose and under steady state conditions (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 307-314 
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    ISSN: 1432-1041
    Keywords: Absorption ; man ; β-methyl-digoxin ; serum concentration ; urinary excretion ; radio-immunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of β-methyl-digoxin 0.4 mg were given to groups of 17 – 18 healthy volunteers as an intravenous infusion lasting 2 hours, or orally as Lanitop Liquidum® or Lanitop® tablets. The serum glycoside concentration and urinary glycoside excretion were measured over 8 and 32 h. The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods. For both periods the area under the serum concentration/time curve and the urinary glycoside excretion were significantly lower after administration of the tablets than after intravenous infusion. Taking the average of both parameters, the absolute bioavailability of β-methyl-digoxin was about 80% from the solution and about 70% from the tablets. In 18 patients undergoing intravenous or oral therapy with β-methyl-digoxin steady state glycoside concentrations were compared in a cross-over study of intravenous maintenance therapy with Lanitop® ampoules or oral treatment with Lanitop® tablets. For a standard daily dose of 0.2 mg β-methyl-digoxin the serum concentrations were 1.35±0.10 ng/ml during both intravenous and oral administration. The intra-individual variation in glycoside concentration after changing from intravenous to oral maintenance therapy, or vice versa, was about the same as during continued intravenous or oral administration. It is concluded that the rate of rise of serum concentration after a single dose may be a useful indicator of the rate of absorption, but that the area under the serum concentration/time curve and the urinary glycoside excretion up to 32 h are unsuitable for determining equivalent doses of different formulations or routes of administration of digitalis glycosides.
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    Metabolism of digitoxin in man and its modification by spironolactone (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 345-354 
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    ISSN: 1432-1041
    Keywords: 3H-digitoxin ; metabolism ; spironolactone ; enzyme induction ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of spironolactone on the metabolism of intravenously administered3H-digitoxin (80 µCi) was investigated in eight patients. In three of them the labelled glycoside was given on a second occasion after spironolactone treatment had been discontinued for at least 65 days. Of total urinary radioactivity 79 % was unaltered drug and 12 % consisted of water soluble compounds. No digitoxigenin or digoxigenin and only trace amounts (〈2 %) of digoxin and the bis- and monoglycosides of digoxigenin were found. After spironolactone total urinary radioactivity was unchanged but the fraction eliminated as unchanged digitoxin fell from 79 to 66 % and the water soluble compounds increased from 12 to 26 % (p〈0.05). In addition spironolactone caused a 20 % reduction in the half-life of serum radioactivity (p〈0.01) and a 16 % reduction in the volume of distribution (p〈0.05). Induction of hepatic enzymes by spironolactone is proposed to explain the alteration in the metabolism of digitoxin in man. Both the altered metabolic pattern and the reduction in the volume of distribution appear to contribute to the reduction in half-life.
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    Some aspects of the intestinal absorption of zinc in man (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 423-428 
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    ISSN: 1432-1041
    Keywords: Serum zinc concentration ; intestinal absorption ; portal vein ; transumbilical catheterization ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum zinc concentrations in peripheral venous blood were determined in 8 healthy volunteers at various times after oral administration of 50 mg Zn++. The same dose was given to 6 patients surgically treated for obesity by jejuno-ileostomy. In the healthy volunteers the mean serum zinc concentration before dosing was 0.89 µg/ml and a mean peak concentration of 2.39 µg/ml was found after 3 h. In the patients the starting level was lower, 0.67 µg/ml, and a mean peak concentration of 1.31 µg/ml was found 90 min after treatment. In the patients the areas under the serum concentration-time curve was approximately 1/3 of that in the healthy subjects. Zn++ 50 mg was also given to 3 patients undergoing transumbilical catheterization of the portal vein for diagnostic purposes and serum zinc concentrations were measured in portal and peripheral venous blood sampled simultaneously. No significant differences were found between the concentration of zinc in portal and peripheral venous blood during absorption, which suggests slow passage of zinc across the intestinal wall.
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    Clinical pharmacokinetics of sisomicin: Two-compartment model analysis of serum data after I.V. and I.M. administration (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 251-256 
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    ISSN: 1432-1041
    Keywords: Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sisomicin, a new single component aminoglycoside antibiotic related to gentamicin c1a, were determined in four healthy volunteers after intravenous and intramuscular administration of a 1 mg/kg dose. The elimination profile of this antibiotic follows two-compartment model kinetics after I.V. administration. The fast (α) and slow (β) disposition rate constants averaged 0.072 and 0.004 min−1, respectively. The volume of distribution at the steady-state averaged 0.185 liters/kg which approximately corresponds to the volume of extracellular space. The physiological availability of an intramuscular dose appeared to be complete. A method of administration adapted to the kinetic properties of the drug is proposed.
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    Double-blind crossover study of the effect of acetylsalicylic acid on bleeding and post-operative course after bilateral oral surgery (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 217-225 
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    ISSN: 1432-1041
    Keywords: Acetylsalicylic acid ; surgery ; man ; bleeding ; pain ; wound-healing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetylsalicylic acid (ASA) was tested against placebo in a double-blind crossover study, in which essentially the same operation was performed twice on 23 healthy patients who required surgical removal of bilateral “identically” impacted wisdom teeth. On the evening before one operation they received ASA 1.0 g (Globentyl®) followed by ASA 2.0 g daily for the next 3 days, and at the other operation placebo tablets. A number of objective and subjective parameters were recorded for paired comparison of the pre-, per-, and post-operative courses, including bleeding, pain, wound-healing, and preference. Tests of platelet aggregation before each operation indicated whether or not ASA had been taken. Pre-operative bleeding time was significantly increased (from 4.4 to 6.9 min) by ASA, as well as the per-operative blood loss (about 30%), and the post-operative bleeding tendency. Episodes of profuse post-operative haemorrhage were reported by 5 patients, always after the operation for which ASA had been given. ASA also significantly promoted the occurrence of ecchymosis and haematoma. The pre-operative bleeding time was not a reliable predictor for these complications. The drug was very well tolerated with respect to side effects such as abdominal discomfort. The post-operative pain scores were neither reduced nor increased significantly by ASA, and the preference scores were not in favour of the drug. The present patients were all young and denied any previous bleeding disorders; nevertheless, ASA resulted in post-operative haemorrhage, ecchymosis and haematoma formation in several cases.
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    URL: http://dx.doi.org/10.1007/BF00558332
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    Pharmacokinetics and bioavailability of indoprofen in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 257-262 
    Details
    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
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    Inhibition of tetracycline absorption by zinc (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 59-62 
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    ISSN: 1432-1041
    Keywords: Tetracycline absorption ; zinc sulphate ; zinc citrate ; complex formation ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The inhibitory effect of zinc on the gastrointestinal absorption of tetracycline has been investigated in 7 healthy volunteers. Zinc (45 mg Zn++) was given as a solution of zinc sulphate and as a zinc citrate complex; tetracycline (500 mg) was administered as a commercially available preparation. Serum tetracycline concentrations and the area under the serum tetracycline concentration-time curve (up to 6 h) were significantly reduced when tetracycline was taken with either zinc sulphate or the zinc citrate complex. Although the reduction of absorption seemed more pronounced after zinc sulphate, the difference between the inhibitory effects of the two forms of zinc was not significant. It is concluded that simultaneous administration of zinc and tetracycline may reduce absorption of tetracycline.
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    URL: http://dx.doi.org/10.1007/BF00561551
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    Effect of analgesic agents on emptying of the gallbladder in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 127-131 
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    ISSN: 1432-1041
    Keywords: Gallbladder emptying ; analgesics ; indoprofen ; pentazocine ; morphine ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A controlled study of the clinical pharmacology of the biliary tract has been made. The rate of gallbladder emptying induced by a fatty meal was taken as a parameter for assessment of the inhibitory effect of indoprofen, a new analgesic-anti-inflammatory drug, pentazocine and morphine. The compounds were administered as single doses by iv (indoprofen and pentazocine) or im (morphine) injection. Indoprofen up to 400 mg had no effect, whereas morphine and pentazocine exerted a significant inhibitory effect on emptying of the gallbladder. Adverse reactions of clinical significance were associated with morphine and pentazocine, but were negligible with indoprofen.
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    URL: http://dx.doi.org/10.1007/BF00609471
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    Plasma dopamine-β-hydroxylase activity and the pressor effect of dopamine infusion in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 197-200 
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    ISSN: 1432-1041
    Keywords: Dopamine-β-hydroxylase ; dopamine infusion ; blood pressure ; plasma ; man ; inter-individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the function of dopamine-β-hydroxylase (DBH) in human plasma, dopamine, its natural substrate, was infused intravenously in 22 healthy volunteers. Their plasma DBH activities showed great interindividual variations (31–301 units/ml). The infusion rates of dopamine required to increase systolic blood pressure (BP) by 30 mm Hg differed considerably between the subjects, and ranged from 3,0 to 11,6 µg/kg/min. No correlation could be shown between the various dopamine doses and individual plasma levels of DBH. It was concluded, therefore, that plasma DBH in the blood stream was enzymatically inactive. Experiments with human plasma DBH in vitro also support this interpretation. Consequently, interindividual differences in the effects on BP during dopamine infusion cannot be due to pressor effects of noradrenaline synthesized by plasma DBH.
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    URL: http://dx.doi.org/10.1007/BF00558329
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    The fate of3H-terbutaline sulphate administered to man as an aerosol (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 1-7 
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    ISSN: 1432-1041
    Keywords: 3H-terbutaline sulphate ; aerosol ; man ; absorption ; excretion ; spirometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six asthmatic patients and two healthy volunteers inhaled tritiated terbutaline sulphate delivered by a pressurized aerosol inhaler. Spirometric measurements were performed and the amounts of total radioactivity in plasma, urine and faeces were determined. The analysis of urine included determination of radioactivity due to metabolized drug. Depending on the amount of drug inhaled the peak plasma level varied from undetectable to 3.8 ng/ml. An early plasma peak was found in 7 out of 8 subjects. The main plasma peaks were observed 1 – 6 hours after administration. The results of urinalysis showed a metabolic profile similar to that after parenteral administration. Disregarding the amount of inhaled drug and sampling time, 3 – 35% of the delivered drug was recovered in the urine and 2 – 37% in the faeces. Immediately after treatment 4 subjects rinsed their mouths with water and it was found to contain 14.5 – 50% of the delivered dose. The adapters from the aerosol canisters contained 14 – 27.5% of the delivered dose of drug.
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    URL: http://dx.doi.org/10.1007/BF00561542
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    Clinical efficacy of BS 100-141 in essential hypertension (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 69-72 
    Details
    ISSN: 1432-1041
    Keywords: BS 100-141 ; N-amidino-2-(2,6-dichlorphenyl)acetamide hydrochloride ; essential hypertension ; antihypertensive agent ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of the guanidine derivative BS 100-141 (N-amidino-2-(2,6-dichlorphenyl)acetamide hydrochloride) has been studied in 11 hospitalized patients suffering from essential hypertension (WHO grade I – II). BS 100-141 1 mg tid was given in the first week and a larger dose in the second week. Mean 24-hour systolic and diastolic blood pressures were significantly lower at the end of the first and second weeks of active treatment than at the end of the placebo-week. The antihypertensive effect of BS 100-141 was stronger in the standing than in the supine position. It significantly reduced the heart rate. Treatment with BS 100-141 was well tolerated, although tiredness and dryness of the mouth appeared more often than during the placebo period. Extensive laboratory tests did not reveal any toxic effect on the liver, kidneys or haemopoietic tissues.
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    URL: http://dx.doi.org/10.1007/BF00561553
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    Comparison of BS 100-141 and clonidine as antihypertensive agents (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 73-76 
    Details
    ISSN: 1432-1041
    Keywords: BS 100-141 ; N-amidino-2-(2,6-dichlorphenyl) acetamide hydrochloride ; clonidine ; essential hypertension ; antihypertensive agents ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect and side effects of the guanidine derivative BS 100-141 (N-amidino-2-(2,6-dichlorphenyl) acetamide hydrochloride) and clonidine were compared in a single-blind, cross-over study. The study consisted of two active treatment periods of 6 weeks each, both preceded by a 2 week placebo period. Thirty ambulant, hypertensive patients, whose blood pressure was of WHO severity grades I – II, were admitted to the study, and the results are based on the 24 patients who completed it. In more than half the patients the optimal daily dose of BS 100-141 was 3 – 4 mg, and of clonidine 0.30 – 0.45 mg. An equally large and significant decrease in blood pressure was produced by both drugs. Both of them also caused bradycardia, but it was of no clinical significance. Both BS 100-141 and clonidine caused tiredness in about half the patients, but it diminished after a few weeks. Dryness of the mouth occurred in more than half the patients taking either drug, and it remained unchanged during the 6 weeks of treatment. A withdrawal syndrome was noted in one patient on discontinuation of clonidine.
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    Observations on the oxidation behavior of Ni-Cr alloys containing minor additions of group III, IV, or V elements (1976)
    Springer
    Oxidation of metals 10 (1976), S. 347-359 
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    ISSN: 1573-4889
    Keywords: oxidation ; nickel-chromium alloys ; Group III–V elements ; reactive minor additions
    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 a number of experimental ternary Ni-15 wt. % Cr-0.5wt. %X alloys (where X= Y, La, Ce, Sm, Th, U, Zr, or V) has been assessed in pure oxygen at 900° C for periods of exposure up to 450 hr, and compared with the behavior of an Ni-15% Cr control alloy. It has been established that while all of the alloys oxidize in accordance with a protective, approximately parabolic regime, considerable differences in oxidation rates are exhibited. In particular, additions of La, Ce, and Th bring about progressively enhanced rates of oxidation relative to the binary alloy, whereas Y, Sm, V, U, and Zr effect increasingly reduced rates of oxidation in the order given. The rate constant for the Th-bearing alloy is about two orders of magnitude larger than that for the alloy containing Zr. Such differences in behavior seem to be associated with subtle variations in the morphology/composition of the corrosion products from alloy to alloy. The observations are considered in the light of earlier published literature concerning the effects of rare-earth and other reactive elements on the oxidation behavior of Ni/Cr alloys.
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    Development, growth, and adhesion of Al2O3 on platinum-aluminum alloys (1976)
    Springer
    Oxidation of metals 10 (1976), S. 189-223 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; platinum ; platinum-aluminum alloys ; alumina (Al2O3) ; oxide-scale adhesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The development, growth, and adhesion of α-Al2O3 scales on platinum-aluminum alloys containing between 0.5 and 6 wt.% aluminum have been studied at temperatures in the interval between 1000 and 1450° C. The morphologies and microstructures of the α-Al2O3 scales were found to be influenced by the temperature, oxygen pressure, and the microstructures of the alloys. The oxidation rates of the alloys appeared to be controlled by transport of oxygen along grain boundaries in the α-Al2O3 scales. The α-Al2O3 scales adhered to the platinum-aluminum substrates even after extensive periods of cyclic oxidation. The good adhesion of the α-Al2O3 may result from mechanical keying of the oxide to the alloys due to the development of irregular oxide-alloy interfaces.
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    The high-temperature oxidation resistance of iron-silicon-aluminum alloys (1976)
    Springer
    Oxidation of metals 10 (1976), S. 277-289 
    Details
    ISSN: 1573-4889
    Keywords: alloy ; iron ; aluminum ; silicon ; oxidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Silicon or chromium can be used as an oxygen getter in iron-aluminum alloys to prevent the internal oxidation of aluminum. This suppresses the formation of the iron oxide nodules that tend to destroy binary iron-aluminum alloys during high-temperature oxidation. Alloys of iron containing aluminum and silicon in varying proportions were heated in flowing air for 50 hr at 1093°C. Of the alloys tested, one containing 6% aluminum and 1 % silicon was the most resistant to oxidation.
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    URL: http://dx.doi.org/10.1007/BF00618248
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    Defect structure in CoO (1976)
    Springer
    Oxidation of metals 10 (1976), S. 311-327 
    Details
    ISSN: 1573-4889
    Keywords: defect structure ; CoO ; 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 total concentration of point defects and deviation from stoichiometry in Co1-yO have been determined experimentally as functions of temperature and equilibrium oxygen pressure in the temperature range 1000–1250°C and oxygen pressure range 10−3-1 atm. This total concentration of defects has also been calculated from known values of the coefficients of chemical diffusion and tracer self-diffusion of cobalt. The results of the two methods agree well. It has been found in the investigated range of temperature and oxygen pressure that the defect structure of cobaltous oxide is composed not only of defects due to deviation from stoichiometry, singly ionized cation vacancies, and an equivalent amount of electron holes, but also of intrinsic defects, probably of the Frenkel type.
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    The influence of platinum on the maintenance of α-Al2O3 as a protective scale (1976)
    Springer
    Oxidation of metals 10 (1976), S. 341-345 
    Details
    ISSN: 1573-4889
    Keywords: α-Al2O3 ; platinum ; oxidation ; adhesion
    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 externally located platinum on the isothermal stability of α-Al2O3 scales formed at high temperatures has been examined. It has been observed that a nickel-base alloy forms an external scale of α-Al2O3 during oxidation at 1200°C, but this scale breaks down isothermally, enabling a faster-growing Cr2O3-rich scale to develop. However, in the presence of platinum metal alongside the specimen in the furnace hot zone, the breakdown of the α-Al2O3 scale is postponed for a substantial period of time. It appears that platinum, as the volatile species PtO2, is incorporated into the growing α-Al2O3 scale where it either influences the stress relief mechanism at temperature or reduces oxidation growth stress generation and thus significantly enhances the isothermal stability of the scale.
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    Electron re-emission Mössbauer study of the oxidation of metallic iron in oxygen (1976)
    Springer
    Oxidation of metals 10 (1976), S. 377-401 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; iron ; Mössbauer ; electron re-emission ; ERM spectroscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The results of an electron re-emission Mössbauer (ERM) spectroscopy study of the oxidation of metallic Fe at temperatures from 150 to 500°C in pure oxygen ( $${\text{p}}_{{\text{O}}_{\text{2}} } \approx {\text{ }}10$$ Torr) are presented. The oxidized samples were prepared from a metallic Fe sample enriched to 70% in the Mössbauer isotope Fe57 and the oxidation kinetics were determined volumetrically. Scanning electron microscopy was employed to characterize the morphology of the oxide films. The hematite, magnetite, and total-oxide thicknesses were determined from the ERM spectra using a theory recently developed in this laboratory, and the results were found to agree well with the measured oxygen content of the oxide films. For Fe and Fe-base alloys it is shown that the ERM technique is most useful in the oxide-thickness range of approximately 20–3000 Å within that range, oxide-phase identifications and thickness determinations are perhaps more readily determined by ERM spectroscopy than by any competing technique. In particular, the ERM measurement is nondestructive, and no supplementary measurements (such as surface-roughness determinations) or special sample preparations (such as oxide-film stripping) are required
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    URL: http://dx.doi.org/10.1007/BF00612049
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    Kinetics of high-temperature oxidation of boron carbide in oxygen (1976)
    Springer
    Oxidation of metals 10 (1976), S. 85-95 
    Details
    ISSN: 1573-4889
    Keywords: boron carbide ; oxidation ; kinetics ; chromatography method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Thermogravimetry and gas-adsorption chromatography were used to study the kinetics of formation of solid and gaseous products during the hightemperature oxidation of compact boron carbide in oxygen at 740 Torr. Oxidation resistance was observed at temperatures up to 1200°C. The main oxidation products were B2O3 and CO2. Oxidation was paralinear; the carbon consumption exceeded the consumption of boron as compared to the ratio of these elements in the compound B4C. This difference resulted in carbon depletion of the carbide layer in the substrate near the scale〉.
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    Microstructures of the scales formed on zircaloy-4 in steam at elevated temperatures (1976)
    Springer
    Oxidation of metals 10 (1976), S. 255-276 
    Details
    ISSN: 1573-4889
    Keywords: Zircaloy-4 ; zirconium ; alloy ; oxidation ; microstructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The ZrO 2 scales formed on Zircaloy-4 PWR tubes during corrosion in steam in the temperature range of 1000–1300°C have been found to contain a metallic phase that is relatively rich in Sn. The precise composition of the metallic phase has not been determined. Most of the metallic phase is located in a line of metallic particles, which is oriented parallel to the alloy-scale interface and located near the center of the scale. The exact morphology of the scale on either side of the particle line has not been identified. The oxide between the metallic particles and the scale-steam interface contains very little Sn, except for a narrow zone adjacent to the scale-steam interface, which was formed in the beginning of the reaction. It appears that the scale between the metallic particles and the alloy-scale interface consists of thin columnar grains of ZrO 2 with a very fine metallic phase probably located at the ZrO 2 grain boundaries. The experimental evidence presently available indicates that the metallic phase exists in the scales at the reaction temperature. If the metallic particles were rich enough in Sn, then a liquid metallic phase would exist in the oxide during the reaction. Kinetic studies demonstrate that these particles move with respect to the scale-steam interface toward the center of the alloy during the course of the oxidation reaction. It appears that the presence of the line of metallic particles could, under certain conditions, markedly influence the mechanical properties of the oxide scales formed on Zircaloy-4.
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    High-temperature oxidation of SiC in a glow-discharge oxygen plasma (1976)
    Springer
    Oxidation of metals 10 (1976), S. 97-103 
    Details
    ISSN: 1573-4889
    Keywords: silicon carbide ; oxidation ; molecular oxygen ; glow-discharge oxygen plasma ; kinetics
    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 kinetics and structure of the oxide scales formed on high-density SiC were studied in molecular oxygen at 740 Torr and in a glow-discharge oxygen plasma at 0.1 Torr at temperatures of 1000, 1100, and 1200°C. The monatomic oxygen formed by the glow discharge markedly increased the reaction rate and the vaporization of some of the oxidation products. The marked differences in kinetics suggest that the rate-controlling step during oxidation in molecular oxygen is the dissociation of adsorbed diatomic oxygen to the monatomic species. Films formed in molecular oxygen were mostly amorphous SiO2 with small inclusions of SiC and graphite, whereas films formed in dissociated oxygen were primarily amorphous SiO2 containing SiO, S2O3, and the coesite form of SiO2.
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    Modification of the oxidation behavior of high-purity austenitic Fe-14Cr-14Ni by the addition of silicon (1976)
    Springer
    Oxidation of metals 10 (1976), S. 1-22 
    Details
    ISSN: 1573-4889
    Keywords: oxidation ; film spalling ; fayalite ; internal 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 oxidation behavior of Fe-14Cr-14Ni (wt.%) and of the same alloy with additions of 1 and 4% silicon was studied in air over the range of 900-1100° C. The presence of silicon completely changed the nature of the oxide scale formed during oxidation. The base alloy (no silicon) formed a thick outer scale of all three iron oxides and an internally oxidized zone of (Fe,Cr,Ni) spinels. The alloy containing 4% silicon formed an outer layer of Cr2O3 and an inner layer of either (or possibly both) SiO2 and Fe2SiO4. The formation of the iron oxides was completely suppressed. The oxidation rate of the 4% silicon alloy was about 200 times less than that of the base alloy, whereas the 1% silicon alloy exhibited a rate intermediate to the other two alloys. The actual ratio of the oxidation rates may be less than 200 due to possible weight losses by the oxidation of Cr2O3 to the gaseous phase CrO3. The lower oxidation rate of the 4% silicon alloy was attributed to the suppression of iron-oxide formation and the presence of Cr2O3, which is a much more protective scale.
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    URL: http://dx.doi.org/10.1007/BF00611695
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    Theoretical study of heterogeneous reaction kinetics: A comparison between microcalorimetric and thermogravimetric curves (1976)
    Springer
    Oxidation of metals 10 (1976), S. 105-111 
    Details
    ISSN: 1573-4889
    Keywords: kinetics ; oxidation ; microcalorimetry ; thermogravimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract In the kinetic theories of Bodenstein or Semenov the expression for the rate of a chemical reaction with several elementary stages can be expressed by different physical parameters. If two experimental methods are used, one method of necessity being microcalorimetry to measure the thermal flux produced by the reaction, it is possible to distinguish a pure kinetics case from a mixed one. The two-method technique has been verified by a study of the oxidation of niobium.
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    Pharmacokinetics of di-n-propylacetate in epileptic patients (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 97-105 
    Details
    ISSN: 1432-1041
    Keywords: Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
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    Correlation between increased dopamine-β- hydroxylase activity and catecholamine concentration in plasma: Determination of acute changes in sympathetic activity in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 181-188 
    Details
    ISSN: 1432-1041
    Keywords: Sympathetic activity ; plasma catecholamine concentration ; dopamine-β-hydroxylase activity ; graded physical exercise ; heart rate ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy untrained volunteers the increase in plasma dopamine-β-hydroxylase (DBH) activity during graded physical exercise has been examined as a true measure of increased activity of the sympathetic nervous system. The correlation between DBH activity, catecholamine concentration (CA) in plasma and heart rate was studied. When work on an electrically braked bicycle ergometer was gradually increased from 12.5 to 100, 200 and 300 watts there was a linear increase in DBH activity and heart rate; the increase in CA concentrations followed an exponential function. The peak values for DBH activity and CA concentration in plasma after the 300 watt work load (as percentages of the resting levels) were 130±3% and 820±71%, respectively; the adrenaline concentration in plasma increased only to 150±19% (p〉0.05). There were significant correlations between heart rate and work load, DBH and work load and log CA and work load. The data imply direct correlations between heart rate and DBH, heart rate and log CA and DBH and log CA. The exponential increase in noradrenaline concentration in plasma might be due either to a greater net “overflow” from sympathetic nerve endings, and/or to increased secretion by the adrenal medulla. In the latter case, the release of noradrenaline would not be accompanied by secretion either of adrenaline or DBH. After work ceased there were sharp falls in heart rate and CA concentration, which indicate an immediate drop in sympathetic activity. DBH activity in plasma returned to normal very slowly; it reached half maximum values after 20 – 22 min. It is concluded that increased sympathetic activity in man can be estimated in vivo as changes in DBH and/or CA concentration in plasma. In contrast, a rapid decrease in sympathetic activity is directly reflected only by a rapid fall in the plasma concentrations of CA.
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    URL: http://dx.doi.org/10.1007/BF00567112
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    Bioavailability of m-octopamine in man related to its metabolism (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 33-39 
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    ISSN: 1432-1041
    Keywords: m-octopamine ; metabolism ; first-pass effect ; man ; enteric absorption ; monohydroxylated phenylalkylamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The diminished sympathomimetic pressor activity of monohydroxylated phenylalkylamines after oral administration has been attributed to incomplete enteric absorption. Therefore, urinary excretion of the unchanged drug and its metabolites has been compared after intravenous and oral administration of3H-m-octopamine to eight patients. Identical amounts of3H-activity (80% of the dose) were excreted after the two routes of dosing, so enteric absorption has been assumed to be complete. Significant differences were found in the fraction of free urinarym-octopamine, which amounted to 10.5% of the dose after infusion and 0.58% after oral administration. The only metabolic pathways form-octopamine are deamination and conjugation. Following oral administration the percentage of conjugates was considerably higher than after intravenous infusion. This metabolic pattern appears typical of all phenylalkylamines with a hydroxyl group in themeta position. Ring hydroxylation to catecholamines was not observed. The enzymes mainly responsible for conjugation after oral administration are located in the gut wall. The resulting “first pass effect”, i.e. metabolism prior to the access to the central compartment, can account for the diminished pharmacodynamic effect after dosing by this route.
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    URL: http://dx.doi.org/10.1007/BF00616412
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  • 84
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    Excretion of norephedrine by man after oral administration of oxyfedrine (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 161-166 
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    ISSN: 1432-1041
    Keywords: Oxyfedrine ; norephedrine ; man ; urinary excretion ; sympathomimetic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of oxyfedrine to healthy volunteers, norephedrine was identified in the urine by thin layer chromatography and gas liquid chromatography and mass spectrography. 30 hours after single oral doses of 8, 16 or 24 mg of oxyfedrine, about 4, 8 and 9 mg, respectively, of norephedrine were found in the urine, i.e. on a molar base 75–100% of the dose was excreted as norephedrine. The peak of excretion occurred within 2–4 hours after administration of the drug. No accumulation of oxyfedrine and/or its metabolite was observed after administration of 16 mg of oxyfedrine t.i.d. for three days. It could not be decided whether oxyfedrine was metabolized to norephedrine by liver enzymes, as in rats, or was spontaneously degraded to norephedrine, e.g. in duodenal fluid before absorption. 30–150 min after oral oxyfedrine (24 mg) norephedrine was demonstrable in duodenal fluid. Thus, in addition to the directβ-sympathomimetic effects of oxyfedrine, it may also have indirect sympathomimetic effects because of the noradrenaline-releasing properties of its metabolite norephedrine.
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    URL: http://dx.doi.org/10.1007/BF00567109
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  • 85
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    Pharmacokinetics and side-effects of clonazepam and its 7- amino-metabolite in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 249-254 
    Details
    ISSN: 1432-1041
    Keywords: Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
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    URL: http://dx.doi.org/10.1007/BF00567123
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  • 86
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    Kinetics of nortriptyline in man according to a two compartment model (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 343-347 
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    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
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    URL: http://dx.doi.org/10.1007/BF00562660
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  • 87
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    Delayed absorption of lithium in intoxication (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 285-285 
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    ISSN: 1432-1041
    Keywords: Lithium ; intoxication ; man ; delayed absorption ; gastric contents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A 55-year old man with lithium intoxication showed increasing serum concentrations in spite of forced diuresis and dialysis. A high lithium content was found in gastric juice three days after the compound had been taken. The serum lithium level began to fall after gastric lavage.
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    URL: http://dx.doi.org/10.1007/BF00567130
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  • 88
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    Plasma concentrations and urinary excretion of the antiarrhythmic quaternary ammonium compound QX-572 in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 277-282 
    Details
    ISSN: 1432-1041
    Keywords: QX-572 ; quaternary ammonium compound ; plasma level ; urinary excretion ; man ; anti-arrhythmic drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N, N-bis (phenylcarbamoylmethyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0±1.1 µg/ml (mean ± SE) at the end of infusion to 3.5±0.5 µg/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7±0.1 µg/ml. In these patients 22±2% (mean±SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.
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    URL: http://dx.doi.org/10.1007/BF00567128
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  • 89
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    Biotransformation and pharmacokinetics of sulfinpyrazone (Anturan®) in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 135-145 
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    ISSN: 1432-1041
    Keywords: Anturan® ; 14C-label ; man ; pharmacokinetics ; biotransformation ; C-glucuronidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2′-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 µg/ml, respectively, after 1 – 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites, i.e. the sulphone G 31 442, the “para-hydroxy”-compound G 32 642 and the “4-hydroxy”-compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as “para-hydroxy”-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as “4-hydroxy”-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-β-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.
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    URL: http://dx.doi.org/10.1007/BF00614010
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  • 90
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    Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 155-159 
    Details
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; benzazepines ; clonazepam ; pharmacokinetics ; gas chromatography ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
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    URL: http://dx.doi.org/10.1007/BF00614012
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    The metabolism of (−)-ephedrine in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 193-198 
    Details
    ISSN: 1432-1041
    Keywords: (−)-[14C]-ephedrine ; metabolism ; urinary excretion ; tolerance ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic fate of orally administered (−)-[14C]-ephedrine has been studied in 3 human subjects and the urinary excretion of metabolites determined quantitatively by solvent extraction, paper chromatography and reverse isotope dilution procedures. Following an oral dose of the drug (0.35 mg/kg, 1.6 µCi), 97% of the dose was excreted in the urine within 48 h, 88% in the first 24 h. Unchanged drug was the major urinary excretory product (53–74%), with N-demethylation occurring to a variable extent (8–20%) although there was little interindividual variation in urine pH. Oxidative deamination was also variable (4–13%); the main identified products of this were benzoic acid (free and conjugated) and 1,2-dihydroxy-1-phenylpropane (free and conjugated). No phenolic metabolites could be detected, and thus it would appear that these compounds cannot be implicated in the acquisition of tolerance to ephedrine which can occur on repeated dosage.
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    URL: http://dx.doi.org/10.1007/BF00614017
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  • 92
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    Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 219-227 
    Details
    ISSN: 1432-1041
    Keywords: Rifampicin ; induction of drug metabolism ; hexobarbital kinetics ; tolbutamide kinetics ; plasma concentrations ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.
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    URL: http://dx.doi.org/10.1007/BF00614021
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    Disposition of quercetin in man after single oral and intravenous doses (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 229-234 
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    ISSN: 1432-1041
    Keywords: Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
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    URL: http://dx.doi.org/10.1007/BF00614022
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  • 94
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    Effects of dixyrazine and methaqualone on the sleep pattern in normal man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 227-231 
    Details
    ISSN: 1432-1041
    Keywords: Dixyrazine ; methaqualone ; etodroxizine ; Isonox® ; sleep stages ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox® (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox® (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone.
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    URL: http://dx.doi.org/10.1007/BF00567120
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    Distribution and elimination kinetics of carbamazepine in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 91-96 
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    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
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    Haemodynamic effects of intravenous disopyramide in heart failure (1975)
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    European journal of clinical pharmacology 8 (1975), S. 167-173 
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    ISSN: 1432-1041
    Keywords: Disopyramide ; haemodynamic effect ; negative inotropic effect ; anticholinergic effect ; hear failure ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of disopyramide have been studied in 11 patients with manifest or imminent heart failure. Disopyramide, 2 mg per kg body weight, was given intravenously during right and left heart catheterisation. The cardiac index decreased by an average of 28% (p〈0.01); mean maximal left and right ventricular end-diastolic pressures were increased by 5.0±0.9 mm Hg (〈0.01) and 5.0±0.6 mm Hg (p〈0.05), respectively; and left ventricular systolic pressure fell slightly but significantly (p〈0.05). No significant change in right ventricular systolic pressure was seen. Pulmonary wedge pressure rose on average by 2.7 mm Hg (p〈0.05). No significant change in heart rate was observed in 5 patients with sinus rhythm. In 6 patients with atrial fibrillation, there was a significant (p〈0.01) increase in heart rate; the average increase in heart rate for the entire group was 19,6 heats per minute. The maximum effect on all the parameters occurred 7–11 minutes after the injection, and it gradually subsided during the following 10 minutes. It was concluded that disopyramide had a potentially serious myocardial depressant effect.
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    Pharmacokinetics of chlormethiazole in humans (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 353-357 
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    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
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    URL: http://dx.doi.org/10.1007/BF00562662
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    Bioavailability studies with Digoxin-Sandoz® and Lanoxin® (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 371-376 
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    ISSN: 1432-1041
    Keywords: Digoxin ; bioavailability ; plasma levels ; cumulative urinary excretion ; particle size ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz® tablets have been compared with Lanoxin® manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to “new” Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.
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    On the pharmacokinetics of proscillaridin A in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 421-425 
    Details
    ISSN: 1432-1041
    Keywords: Proscillaridin ; enteric-coated tablets ; plasma levels ; urine excretion ; 86Rb-erythrocyte assay ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration of proscillaridin was measured by a modified86Rd method during treatment with multiple doses of a commercial preparation of proscillaridin. Despite high doses, very low plasma levels were found, and there were only minute amounts of glycoside activity in urine and faeces. Administration of an enteric-coated proscillaridin preparation gave higher plasma levels, which raises the possibility of inactivation of the glycoside by acid gastric juice. The results suggest that proscillaridin has low biological availability when given orally, and that it is extensively metabolised in the body.
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    URL: http://dx.doi.org/10.1007/BF00562316
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  • 100
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    Haemodynamic effects of intravenous verapamil at rest and during exercise in subjectively healthy middle-aged men (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 317-322 
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    ISSN: 1432-1041
    Keywords: Verapamil ; haemodynamics ; exercise ; man ; vascular resistance ; negative inotropism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Verapamil, 0.1 mg/kg body wt, was injected i.v. over 2 minutes in 8 subjectively healthy middle-aged men, followed by a continuous infusion of 0.007 mg/kg body wt per minute. Prior to the injection several of the subjects had raised pulmonary or systemic arterial pressures. At rest, the central pressures increased slightly, which was taken as a sign of a moderate negative inotropic effect, but there was no change in pre-ejection period or maximal dp/dt of the aortic pressure. The heart rate increased and there was a small decrease in systemic arterial pressure, probably due to a fall of systemic vascular resistance. The PQ time was prolonged. During exercise, with its positive inotropic stimulation, the moderate negative inotropic effect of verapamil disappeared, whereas the increase in heart rate and decrease in aortic pressures persisted. Some variables that reflected the oxygen demand of the heart decreased. The slight negative inotropic effect does not appear to be a particular contraindication to the use of verapamil, but it should be employed cautiously in conditions with a compensatory rise in systemic vascular resistance, or if atrioventricular conduction is impaired.
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    URL: http://dx.doi.org/10.1007/BF00562656
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