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  • 1
    Electronic Resource
    Electronic Resource
    Enhanced drug metabolism after sulfinpyrazone treatment in patients aged 50 to 60 years (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 1409-1413 
    Details
    ISSN: 1432-1440
    Keywords: Sulfinpyrazone ; Drug metabolism ; Enzyme induction ; Sulfinpyrazon ; Arzneimittelmetabolismus ; Enzyminduktion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Sulfinpyrazon (Anturano) wird als Uricosuricum wie als Thrombozytenaggregationshemmer meist gleichzeitig mit anderen Medikamenten verabreicht. Die Kenntnis möglicher Einflüsse auf den Arzneimittelstoffwechsel ist für eine sichere medikamentöse Therapie unerläßlich. Deshalb wurde bei fünf Patienten mit einer Indikation für die Sulfinpyrazon-Therapie der Einfluß einer täglichen Gabe von 800 mg Sulfinpyrazon über 4 Wochen auf den hepatischen Arzneimittelstoffwechsel überprüft. Als Parameter für eine Steigerung des Arzneimittelmetabolismus war die Antipyrin-Plasma-Halbwertszeit bei allen Patienten verkürzt, im Mittel von 12,3±3,9 auf 7,8±2,0 h und die Antipyrin-Clearance von 39,0±16,0 auf 57,6±13,7 ml/min gesteigert. Erwartungsgemäß konstant blieb das Verteilungsvolumen mit 38,0±8,6 bzw. 37,4±5,71. Die Urin-Ausscheidung von 6-β-OH-Cortisol stieg von 65,0±025,7 auf 346,8±193,4 µg/24 h an und das Verhältnis 6-β-OH-Cortisol/freies Cortisol von 4,1 auf 15,8. Nach dreiwöchiger Behandlung war die GGT von 174,±4,9 auf 32,6±12,5 U/l erhöht. Die Ergebnisse zeigen, daß eine Behandlung mit Sulfinpyrazon auch bei 50–60jährigen Patienten zu einer Induktion des Arzneimittelstoffwechsels führt. Vor allem bei gleichzeitiger Gabe mit oralen Antikoagulantien sollte dies neben der initialen Verstärkung des Antikoagulantieneffektes berücksichtigt werden.
    Notes: Summary The induction of liver drug metabolism was investigated in five patients before and after the administration of 800 mg sulfinpyrazone daily for 4 weeks, by using antipyrine plasma-pharmacokinetics and by determining urinary excretion of 6-β-OH-cortisol and serum gamma-glutamyl-transpeptidase (GGT) activity. Antipyrine half-life was shortened in all patients from a mean value of 12.3±3.9 h to 7.8±2.0 h and antipyrine clearance was increased from 39.0±16.0 ml/min to 57.6±13.7 ml/min. In contrast the volume of distribution of antipyrine was unaffected; the values being 38.0±8.6 liters and 37.4±5.7 liters, respectively. In all patients the excretion of 6-β-OH-cortisol in the urine went up from 65.0±25.7 µg/24 h to 346.8±193.4 µg/24 h. The ratio 6-β-OH-cortisol/free cortisol changed from 4.1 to 15.8. After 21 days of treatment the GGT increased from 17.4±4.9 units/liter to 32.6±12.5 units/liter The data presented confirm that sulfinpyrazone induces drug metabolism in patients of the older age group. Interactions between sulfinpyrazone and other drugs given simultaneously must be borne in mind.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716246
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  • 2
    Electronic Resource
    Electronic Resource
    Nonlinear plasma spectroscopy of the hydrogen balmer-α line (1983)
    Springer
    Applied physics 32 (1983), S. 63-73 
    Details
    ISSN: 1432-0649
    Keywords: 52.70 Kz ; 52.25 Lp ; 52.80 Ng ; 42.65 Gv
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The plasma line broadening of Hα fine-structure lines is investigated with Doppler-free saturation and polarization spectroscopy in He-H gas and are discharges at plasma densities of 108 cm−3 〈N≲1.4×1014 cm−3. With a single-mode laser, the shift and broadening of four resolved Hα fs lines are measured in a low pressure discharge forN〈1011 cm−3. With an intense, broadband multi-mode laser the plasma effects of Hα are investigated up toN=1.4×1014 cm−3 in a hollow cathode are. Calculations in the classical phase shift and impact approximations can explain the experimental data and peculiarities of the low-density plasma effects and show that the ions are the dominant perturbers. Ion dynamical effects, perturber mass and temperature dependence, are observed and interpreted. Applications of the nonlinear techniques to other H and D lines, other atoms, and for H and D plasma diagnostics are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688545
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  • 3
    Electronic Resource
    Electronic Resource
    The clinical pharmacokinetics of buflomedil in normal subjects after intravenous and oral administration (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 459-463 
    Details
    ISSN: 1432-1041
    Keywords: buflomedil ; vasodilatation ; pharmacokinetics ; bioavailability ; vasoactive drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose-ranging pharmacokinetic study of buflomedil was carried out in eight subjects to determine the pharmacokinetic parameters of the drug after oral and intravenous administration. Based on AUC∞ analyses, the pharmacokinetics of buflomedil were found to be linear within the dose ranges studied (50 to 200 mg for i. v. injection and 150 to 450 mg for oral administration). In the oral study, the mean biological half-life of the drug was 2.97 h, while after intravenous dose it was 3.25 h. The apparent volume of distribution after the pseudodistribution equilibrium (Fdβ) and volume of distribution at the steady state (Vdss) were 1.43±0.24 l/kg and 1.32±0.26 l/kg, respectively. The mean urinary recovery of intact drug and the metabolite, paradesmethyl buflomedil, after intravenous dosing, were 23.6% and 18.7%, respectively, while after oral dosing, they were 18% and 14.8%, respectively. On the average, 72% of the dose was obserbed into the systemic circulation after oral administration. This level of bioavailability was attributed to the hepatic first-pass effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542100
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  • 4
    Electronic Resource
    Electronic Resource
    Elimination of azlocillin in patients with biliary t-tube drainage (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 435-439 
    Details
    ISSN: 1432-1041
    Keywords: azlocillin ; kinetics ; biliary excretion ; liver dysfunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic of azlocillin was followed in five elderly patients after biliary surgery. Total clearance was 138.6±17.7 ml/min when 2.0 g was given as an i.v. bolus injection. The half-life of the β-phase averaged 110 min. The total clearance and the half-life of azlocillin were influenced by slight impairment of renal function (creatinine clearance 59.4±13.6 ml/min). In patients with normal liver function biliary excretion of the drug amounted to 5.3±2.8% of the dose (n=3) and the kinetics of biliary excretion were linear. In contrast, in two patients with impaired liver function biliary excretion was 0.2% and 0.5% of the dose, and kinetic analysis of biliary excretion rates revealed at least one zero order step in the excretion process. Renal excretion of the drug amounted to 45.0±17.7% of the dose, which means that 50% of the total clearance of azlocillin has to be accounted for by metabolic clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542549
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  • 5
    Electronic Resource
    Electronic Resource
    Lack of effect of cimetidine on action of phenprocoumon (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 365-367 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; phenprocoumon ; warfarine ; drug metabolism interaction ; histamine receptor antagonist ; anticoagulation ; bleeding complication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In patients on oral warfarin, nicoumalone and phenindione an increase in the anticoagulant effect has been described during concomitant treatment with cimetidine. Therefore the effect of cimetidine on the steady state dynamics of phenprocoumon has been investigated in ten outpatients. No change in the anticoagulant effect of phenprocoumon was observed during or after two weeks on cimetidine, as measured by the thrombotest coagulation method, prothrombin time, fibrinopeptide A concentration and plasma phenprocoumon level. The data show that cimetidine does not interact with the metabolism of phenprocoumon in contrast to warfarin. Thus, phenprocoumon maintenance therapy when combined with concomitant cimetidine treatment can be considered not to carry an increased risk of haemorrhagic complications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613622
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  • 6
    Electronic Resource
    Electronic Resource
    Structure of oxy- and deoxy-erythrocruorin at 1.4 Å resolution (1980)
    Springer
    European biophysics journal 6 (1980), S. 58-58 
    Details
    ISSN: 1432-1017
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00647531
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  • 7
    Electronic Resource
    Electronic Resource
    Non-linear elimination processes of theophylline (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 71-78 
    Details
    ISSN: 1432-1041
    Keywords: nonlinear kinetics ; theophylline ; dimethyluric acid ; theophylline metabolism ; 1-methyluric acid ; 3-methylxanthine ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After intravenous and oral administration of theophylline to four healthy subjects, the plasma concentration-time curve of theophylline could be described by linear pharmacokinetics, although total clearance in all subjects decreased when the dose was increased; the doses were theophylline 193.2 mg and 386.4 mg i.v. and 161 mg and 322 mg p.o. Total clearance was 65.5±11.3 ml/min. Renal clearance changed from 15.2±9.5 ml/min in the first two hours after administration to 4.9±5.5 ml/min between 16 and 24 h (p〈0.001). 1,3-dimethyluric acid (DMU), the major metabolite of theophylline, was determined in urine and in plasma. The renal clearance of DMU was constant at 496.7±180 ml/min. There was some evidence that at high plasma concentrations of theophylline the formation of DMU might be a zero-order process. The renal excretion rate of 1-methyluric acid (1-MU) paralleled that of DMU, which is in accordance with the assumption that DMU is demethylated to 1-MU. 3-methylxanthine (3-MX) was excreted in urine at a constant rate over 10 h, the rate being equivalent to the dose, which is contrary to the assumption of Michaelis-Menten-kinetics. 3-methyluric acid was found to be a minor metabolite of theophylline and 1-methylxanthine (1-MX) could not be detected. The cumulative amounts excreted in urine, expressed as a percentage of the dose and corrected for molecular weight, were theophylline 16.6±6.5%, DMU 44.3±7.0%, 1-MU 24.3±4.8%, 3-MX 12.9±3.4% and 3-MU 2.2±1.8%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613930
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  • 8
    Electronic Resource
    Electronic Resource
    Lack of clinically important interaction between erythromycin and theophylline (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 485-489 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; erythromycin ; interaction ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8±4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4±9.9 vs 63.8±14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7±2.6 vs 7.5±1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4±5.0 vs 42.1±5.4% 1,3-dimethyluric acid, 29.6±4.6 vs 30.1±5.9% 1-methyluric acid and 13.4±3.5 vs 12.5±2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542146
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  • 9
    Electronic Resource
    Electronic Resource
    Intestinal absorption of levodopa in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 69-72 
    Details
    ISSN: 1432-1041
    Keywords: levodopa ; intestinal absorption ; small intestine ; bioavailability ; benserazide ; presystemic clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In four healthy subjects the intestinal absorption of levodopa (l-dopa) was investigated by measuring the plasma concentration of the amino acid following the administration of l-dopa at three different sites in the small intestine. In order to minimize presystemic clearance of l-dopa, the subjects were pretreated with the peripheral decarboxylase inhibitor benserazide 3×50 mg every 8 h on the previous day and 1×50 mg 2 h prior to administration of the l-dopa. L-dopa 100 mg dissolved in 0.05 N HCl and 50 mg benserazide dissolved in 0.05 N HCl were coadministered. Under these conditions no difference in tmax, cmax or AUC of l-dopa was observed between administration of the drug into the proximal or the distal part of duodenum, or into the upper part of jejunum. The results indicate that in healthy subjects, during inhibition of peripheral decarboxylase, the rate and extent of l-dopa absorption does not differ at any site in the upper small intestine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544017
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of single and multiple doses of sulphinpyrazone on antipyrine metabolism and urinary excretion of 6-beta-hydroxycortisol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 797-801 
    Details
    ISSN: 1432-1041
    Keywords: sulphinpyrazone ; drug metabolism ; enzyme induction ; 6-beta-hydroxycortisol antipyrine ; antipyrine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sulphinpyrazone decreases the plasma clearance of tolbutamide and S-warfarin and increases the clearance of R-warfarin, theophylline and antipyrine. In order to determine whether sulphinpyrazone is an inducer or inhibitor or both of oxidative drug metabolism, antipyrine and its metabolites as well as 6-beta-hydroxycortisol were measured in urine before, 24 h and after 23 days of chronic administration of sulphinpyrazone (4×200 mg/day). During chronic treatment sulphinpyrazone increased the ratio of 6-beta-hydroxycortisol to the 17-hydroxycorticosteroids by 70% (p〈0.02). The renal clearance of the main oxidative metabolites of antipyrine (4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine) were increased after sulphinpyrazone (p〈0.02). Except for norantipyrine, no change in total excretion of antipyrine and its metabolites occurred after 24 h or after 23 days. It is concluded that sulphinpyrazone induces the enzymes which metabolize antipyrine and cortisol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542523
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