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  • Springer  (324)
  • Wiley-Blackwell  (10)
  • 11
    Electronic Resource
    Electronic Resource
    Polymorphic flecainide disposition under conditions of uncontrolled urine flow and pH (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 155-162 
    Details
    ISSN: 1432-1041
    Keywords: Flecainide ; sparteine/debrisoquine polymorphism ; metabolism ; enantiomers ; pharmacokinetics ; stereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of R- and S-flecainide have been determined in five poor (PM) and five extensive (EM) metabolisers of sparteine/debrisoquine under conditions of uncontrolled urine flow and pH. The half-lives of R- and S-flecainide in PMs (R 19.3 h; S 16.1 h) were approximately twice those observed in EMs (R 8.8 h; S 9.1 h). The apparent oral clearances of R- and S-flecainide were lower in PMs (R 313 ml·min−1; S 379 ml·min−1) than in EMs (R 783 ml·min−1; S 828 ml·min−1). The renal clearance, however, was comparable for both enantiomers in both EMs and PMs, and therefore the phenotypic differences in flecainide disposition observed must be due to differences in metabolic clearance. The nonrenal clearance of both enantiomers was significantly lower in poor (R 123 ml·min−1; S 201 ml·min−1) relative to extensive metabolisers (R 533 ml·min−1; S 586 ml·min−1). The partial clearance to the two major metabolites meta-O-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of flecainide (MODLF) was significantly lower in poor (62 ml·min−1) than extensive (267 ml·min−1) metabolisers. The impairment in flecainide metabolism in poor metabolisers of sparteine/debrisoquine has therefore been confirmed. Under conditions reflecting the clinical situation the difference in disposition between EMs and PMs would be considerable. However, it may be predicted that at standard doses concentrations greater than 1000 ng·ml−1 would not be attained in the PMs studied. The serum protein binding of R- and S-flecainide was studied in each subject and no differences between the enantiomers or the phenotypes were observed (Free fraction EM: R 0.43; S 0.42; PM R: 0.46; S: 0.46). Enantioselective disposition was noted in all PMs studied, due to a significantly lower nonrenal clearance of the R-enantiomer. In extensive metaboliser subjects, considerable interindividual variation in the enantioselective disposition of flecainide was noted, ranging from metabolism favouring either enantiomer to the absence of any selectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280070
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  • 12
    Electronic Resource
    Electronic Resource
    Plasma levels of sulfinpyrazone and of two of its metabolites after a single dose and during the steady state (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 231-235 
    Details
    ISSN: 1432-1041
    Keywords: sulfinpyrazone ; pharmacokinetics ; metabolites ; inhibition of platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulfinpyrazone, and the plasma levels of its sulfide and sulfone metabolites, have been determined after a single oral dose (400 mg) and during steady-state conditions (4×200 mg daily for 6 days) in healthy female volunteers. The plasma half-lives of sulfinpyrazone, the sulfone and the sulfide were 3.7, 3.2 and 14.7 h, respectively, during steady-state. After a single dose and during steady state conditions the half-lives of sulfinpyrazone and the sulfone did not differ significantly. The trough plasma levels of the sulfide metabolite exceeded those of the parent compound in four of the six volunteers on the last day of the study. The data suggest that in man the most likely candidate for the prolonged inhibition of platelet aggregation observed after treatment with sulfinpyrazone is its sulfide metabolite, because of its prolonged elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613823
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  • 13
    Electronic Resource
    Electronic Resource
    Disposition of 5-aminosalicylic acid, the active metabolite of sulphasalazine, in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 511-515 
    Details
    ISSN: 1432-1041
    Keywords: 5-aminosalicylic acid ; inflammatory bowel disease ; sulphasalazine disposition ; pharmacokinetics ; healthy volunteers ; urinary excretion ; biliary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of 5-aminosalicylic acid (5-AS), the therapeutically active metabolite of sulphasalazine (SZ), has been studied in patients with active inflammatory bowel disease, in patients with biliary tract disease and post-operative T-tube drainage, and in healthy volunteers. Subjects were treated 3 times a day either with 5-AS 0.5 g suppositories and a slow-release preparation or with SZ 1 g tid (equivalent to 5-AS 1.14 g/day). Plasma and urine concentrations of 5-AS and its acetylated major metabolite (AcAS) were monitored during one dosing interval. In a cross-over trial in 5 patients with ulcerative colitis no difference, was found in the dose-corrected mean (± SD) steady state plasma levels (Css) of 5-AS and AcAS between treatment with 5-AS suppositories (0.10±0.07 and 0.50±0.20 µg/ml, respectively) and SZ (0.12±0.14 and 0.67±0.14 µg/ml, respectively). Urinary excretion of total AS (5-AS+AcAS), too, was similar (192±70 and 179±79 mg/day) with both forms of treatment. The oral slow-release form of 5-AS produced slightly higher Css in 5 patients with Crohn's disease (5-AS 0.21±0.22 µg/ml; AcAS 0.83±0.40 µg/ml) and in 5 healthy volunteers (5-AS 0.28±0.14 µg/ml; AcAS 1.10±0.43 µg/ml). Urinary recovery of total AS averaged 20±6% (patients) and 27±10% (volunteers). The cross-over trial in 7 patients with a biliary T-tube revealed that after single doses of 5-AS 1 g and SZ 2 g between 0.01% and 0.75% could be recovered in collected bile (85–500 ml/day) as total AS (traces of free 5-AS, and acetylated and glucuronidated 5-AS), indicating some enterohepatic circulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542120
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  • 14
    Electronic Resource
    Electronic Resource
    Estimation of the absolute bioavailability of flecainide using stable isotope technique (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 51-55 
    Details
    ISSN: 1432-1041
    Keywords: Flecainide ; Bioavailability ; stable isotope ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Data on the absolute bioavailability of flecainide are controversial. We have investigated whether differences in metabolic clearances and/or the absorption profile might be responsible for the variability in its absolute bioavailability. Six subjects with a wide range of flecainide metabolic clearances (85–407 ml·min−1) simultaneously received the drug by the IV and oral routes; the oral dose was labelled with deuterium. Besides estimation of absolute bioavailability, this design permitted assessment of metabolic clearance after IV and oral administration, and absorption could be assessed from the urinary excretion of labelled and unlabelled drug and metabolites. The absolute bioavailability of flecainide ranged from 79.9 to 101.1% (mean 93.6%). The absorption was 86.1 to 101.3% (mean 93.2%). The data indicate that the variable bioavailability of flecainide is due both to metabolism and absorption. The study highlights the potential of stable isotope technique in the investigation of such issues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00202172
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  • 15
    Electronic Resource
    Electronic Resource
    Treatment of parkinsonism with L-DOPA in association with a decarboxylase inhibitor (1969)
    Springer
    European journal of clinical pharmacology 2 (1969), S. 23-26 
    Details
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Attempts to treat Parkinson's disease with L-DOPA have led to a turning-point in the therapy of this disease, akinesia responding particularly well to this drug. The high doses of L-DOPA which are necessary to improve the clinical condition are not free from disadvantages. The combination with the decarboxylase inhibitor Ro 4-4602 allows a considerable reduction of the effective dose of L-DOPA, the results being equally satisfactory. A pilot study involving 10 treated patients was conducted to compare the effects of L-DOPA alone and of the combination with Ro-4-4602. Objective assessment was obtained with the help of psycho-physiological senso-motor tests which are briefly described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404181
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  • 16
    Electronic Resource
    Electronic Resource
    Influence of intravenous acetylsalicylic acid and sodium salicylate on human renal function and lithium clearance (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 435-441 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; sodium salicylate ; renal function ; lithium clearance ; cyclooxygenase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of intravenous acetylsalicylic acid (ASA; D,L-lysine-mono-acetylsalicylate), equimolar doses of sodium salicylate (SA) and placebo (P) on renal function has been studied in 6 healthy female volunteers, in 150 mmol sodium balance, and in lithium (Li) steady state with a plasma Li between 0.6 and 0.8 mmol/l. Following a bolus injection of 0.5 g ASA, 0.444 g SA or P (50 ml saline) given over 10 min and a subsequent continuous infusion of 1.5 g ASA, 1.332 SA or P (150 ml saline) over 170 min, urine was collected for 3 h as well as 6 plasma samples at 30-min intervals. Plasma ASA levels were between 13.8 and 22.1 µg/ml and for SA they were 20.8 to 82.6 µg/ml during ASA infusion, and between 22.5 and 108.9 µg/ml for SA during SA infusion. Neither ASA nor SA caused a significant change in urine volume, in the renal clearances of Na, K, free water, osmolality, creatinine, inulin and p-aminohippurate (PAH) or in plasma Li level. Renal Li clearance was slightly reduced by SA, from 37.8 to 29.4 ml/min (p〈0.05). Since renal prostaglandin (PG) synthesis (urinary PGE2 excretion) was 60.6% suppressed by ASA and was not affected by SA, the decrease in Li clearance cannot be related to inhibition of cyclooxygenase in the kidney.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613458
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  • 17
    Electronic Resource
    Electronic Resource
    The rhabdom structure in the ommatidia of the Heteroptera (Insecta), and its phylogenetic significance (2000)
    Springer
    Zoomorphology 120 (2000), S. 1-13 
    Details
    ISSN: 1432-234X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  In its plesiomorphic state the insect ommatidium consists of eight retinula cells forming a fused rhabdom. It has long been observed that, in contrast to this pattern, Heteroptera have open rhabdoms. However, there has so far been no comprehensive and comparative study of heteropteran ommatidia. For this reason, we investigated the rhabdom structure in 36 species from all higher groups of Heteroptera, as well as from Coleorrhyncha and Auchenorrhyncha as outgroup representatives. In addition we surveyed the data of earlier authors, which brings the number of examined species to a total of more than 70. All examined Heteroptera do have open rhabdoms, with a system of six peripheral and two central rhabdomeres. Outgroup comparison shows that the open rhabdom is an autapomorphy of the Heteroptera. As for the rhabdom structure within the Heteroptera, we found further autapomorphic patterns in Corixidae (Nepomorpha), Gerromorpha, and Leptopodomorpha. Finally, the Cimicomorpha and Pentatomomorpha share a special pattern of the two central rhabdomeres, which we call V-pattern. This is a new synapomorphy of these two taxa.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004359900018
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  • 18
    Electronic Resource
    Electronic Resource
    Energy sensitive detection of heavy ions with transition edge calorimeters (1993)
    Springer
    Journal of low temperature physics 93 (1993), S. 231-238 
    Details
    ISSN: 1573-7357
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Status and results of a research project are reported, which aims at developing calorimetric low temperature detectors for heavy ions. The special conditions for the detection of energetic heavy ions are discussed. The response of an aluminium transition edge calorimeter, operated at about1.5K, to the impact of heavy ions was investigated. The observed energy resolutions ΔE/E=3.9×10−3for5.9MeV/u 208 Pb-ions, ΔE/E=1.6×10−3for4.8MeV/u 58 Ni-ions and ΔE/E=4.3×10−3for100MeV/u 20 Ne-ions are most probably not yet limited by the intrinsic detector resolution. The present results already represent an improvement over conventional solid state detectors and ionization chambers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00693425
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  • 19
    Electronic Resource
    Electronic Resource
    Heavy metals (Cu, Zn, Pb, Cd) in sediment, zooplankton and epibenthic invertebrates from the area of the continental slope of the Banc d'Arguin (Mauritania) (1993)
    Springer
    Hydrobiologia 258 (1993), S. 41-58 
    Details
    ISSN: 1573-5117
    Keywords: heavy metals ; sediment ; zooplankton ; epibenthic invertebrates ; Banc d'Arguin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The concentrations of copper, zinc, lead and cadmium in the surface sediment (upper 5 mm) were generally higher in the silt fraction than in the bulk sediment. No significant geographical trend in the metal concentrations of the surface sediments was found, nor a correlation between concentrations in bulk sediment as well as in the silt fraction and the % silt could be established. In general, the metal concentrations in both bulk sediment and silt are lower, when compared to marine environments in other climatological regions. In zooplankton, the metal concentrations were relatively high: expressed in µg g−1 on a dry weight (D.W.) basis, they ranged from 15–90 for copper, 70–580 for zinc, 12–55 for lead and 4–10 for cadmium. In epibenthic invertebrate species, both in crustaceans and bivalve molluscs, the concentrations of copper, zinc, and lead were in the same order of magnitude as compared to corresponding species from other geographical latitudes. Cadmium concentrations were relatively low, ranging from 0.13–0.42 µg g−1 D.W. in the bivalve molluscs Pitaria tumens and from 0.04–0.27 µg g−1 D.W. in the shrimp Processa elegantula. Also in the crab species Ilia spinosa, Inachus sp. and Pagurus sp., the cadmium concentrations were low, varying between 0.1 and 0.2 µg g−1 D.W. No significant relation between the metal concentration in whole-body samples and sediment (either bulk or silt) was present. Also no gradient was apparent in concentrations in organisms sampled at different depths (5 to 200 m) along two off-shore transects perpendicular to the Banc d'Arguin. Data indicated lower metal concentration in epibenthic organisms from sampling stations along a northern transect (southwest of Cap Blanc) than in organisms from the southern transect, off Cap Timiris. Evidence was obtained for a considerable atmospheric input of heavy metals, in particular zinc and lead, in a certain area along the continental slope of the Banc d'Arguin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00006185
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  • 20
    Electronic Resource
    Electronic Resource
    Determination of complexation equilibria of macromolecules with small molecules by means of size exclusion chromatography (1994)
    Springer
    Polymer bulletin 33 (1994), S. 339-346 
    Details
    ISSN: 1436-2449
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Summary A new size exclusion chromatographic procedure for determination of complexation of macromolecules with low molar mass substances (such as preferential solvation or drug-protein-binding) was proposed. The method is based on the assessment of system peaks formed as result of differences between eluent composition and bulk solvent composition due to the complexation within the initial sample solution. The composition of the eluent, which contains the same components as the sample solvent, is adjusted in such a way that the system peak disappears. Under these circumstances the bulk solvent composition equals to the eluent composition and the former can be easily calculated. This procedure was tested by measuring the preferential solvation in a model system polystyrene plus toluene plus methanol and by comparing the result with the data obtained with two other chromatographic methods.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314272
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