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  • 1
    Electronic Resource
    Electronic Resource
    Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 1401-1407 
    Details
    ISSN: 1432-1440
    Keywords: Drug Interaction ; Cimetidine ; Metoprolol, propranolol, atenolol ; Chronic treatment ; Arzneimittelinteraktion ; Cimetidin ; Metoprolol, Propranolol, Atenolol ; Chronische Therapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Pharmakokinetik von Metoprolol, Propranolol und Atenolol wurde nach jeweils 7tägiger oraler Monotherapie mit diesen Substanzen und nach 7tägiger kombinierter Gabe jedes Betablockers zusammen mit Cimetidin bei 6 gesunden Probanden geprüft. Cimetidinapplikation führte zu keiner Änderung des kinetischen Verhaltens von Atenolol. Demgegenüber stiegen nach Cimetidingabe die maximalen Metoprolol-Plasmaspiegel durchschnittlich um 70% und die von Propranolol um 95% im Vergleich zur Monotherapie mit diesen beiden Betablockern an (P〈0,05). Ähnlich verhielt sich die AUC beider Betablocker unter zusätzlicher Therapie von Cimetidin (P〈0,05). Bis auf einen geringen, jedoch nicht signifikanten Anstieg der Eliminationshalbwertzeit von Metoprolol und Propranolol bei gleichzeitiger Cimetidingabe wurden andere kinetische Parameter dieser beiden Pharmaka durch Cimetidin nicht bemerkenswert verändert. Die am 6. Tag jeder Behandlungsphase gemessene Hemmung der belastungsabhängigen Tachykardie ergab keine signifikanten Unterschiede zwischen der Monotherapie mit den jeweiligen Betablockern und deren kombinierter Gabe mit Cimetidin. Außer einem Probanden, der am 6. Tag der Therapie mit Metoprolol und Cimetidin über Angstgefühl, Schwäche und Schweißausbruch klagte, wurden weder in der Behandlungsperiode von Cimetidin mit den 3 Betablockern noch in den Monotherapiephasen Nebenwirkungen beobachtet.
    Notes: Summary Pharmacokinetics of metoprolol, propranolol, and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs, and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (P〈0.05). The plasma level time curve (AUC) of the two above-mentioned beta blockers behaved similarly (P〈0.05). Other kinetic parameters of these two drugs were not influenced to a statistically significant extent by cimetidine, despite the tendency for the elimination half-life of metoprolol and propranolol to be prolonged when cimetidine is added. Measurement of exercise-induced tachycardia on the sixth day of administration showed no differences between monotherapy with the beta blockers and combined treatment with each of them together with cimetidine. Apart from one volunteer who complained of anxiety, weakness, and sweating on the sixth day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers, nor during monotherapy with beta blockers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716245
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  • 2
    Electronic Resource
    Electronic Resource
    Plasma salicylate levels and platelet function after acute and chronic administration of slow-release acetylsalicylic acid (Monobeltin) (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 683-687 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; slow-release-formulation ; platelet function ; plasma salicylates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationships between the antiplatelet effects and the pharmacokinetics of a slow release formulation of acetylsalicylic acid (ASA) have been investigated. After acute intake of 750 mg ASA in a slow-release formulation (Monobeltin), a slow increase in plasma ASA was paralleled by a gradual decrease in certain platelet functions. During chronic medication (750 mg twice daily), ASA was present in plasma at all times accompanied by full inhibition of platelet aggregation. For chronic antiplatelet therapy, this slow release formulation of ASA appears to be very effective, unless rapid inhibition of platelet function must be achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547049
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  • 3
    Electronic Resource
    Electronic Resource
    Penbutolol: Pharmacokinetics, effect on exercise tachycardia, and in vitro inhibition of radioligand binding (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 613-623 
    Details
    ISSN: 1432-1041
    Keywords: penbutolol ; beta-adrenoceptor blockade ; pharmacokinetics ; pharmacodynamics ; in vitro/in vivo correlation ; radioreceptor assay ; active metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of penbutolol 40 mg, its reduction in exercise-induced tachycardia, and the in vitro inhibition of radioligand binding to beta-adrenoceptors by plasma have been investigated in 7 healthy volunteers. The peak penbutolol concentration of 285 ng/ml was observed 1.2 h after administration, and the maximum of 4′-OH-penbutolol of 4.76 ng/ml was found after 1.64 h. Penbutolol was detected for up to 48 h, and 4′-OH-penbutolol dropped below the limit of detection after about 10 h. The terminal plasma concentration of penbutolol declined with an average half-life of 19 h. The maximum reduction in exercise-induced tachycardia was 33 beats/min 2.6 h after taking penbutolol. There was still a significant reduction of about 7 beats/min after 48 h. This effect could be adequately explained by the concentration-time course of penbutolol in combination with Clark's model of the concentration-effect relationship. Antagonist activity in plasma caused 91% inhibition of radioligand binding in vitro to beta2-adrenoceptors on rat reticulocyte membranes 1.6 h after intake of penbutolol. By 48 h after intake, radioligand binding was still significantly inhibited (23%). The in vitro inhibition of radioligand binding by plasma showed a linear correlation with the reduction in exercise-induced tachycardia for all phases of the workload. The time course of the reduction in heart rate was completely explained by the in vitro inhibition of radioligand binding. However, it was not possible to explain the in vitro inhibition of radioligand binding by the concentration-time course of penbutolol using a simple competition model, although both variables were based on the same sampling site. When the in vitro inhibition of radioligand binding was plotted against the penbutolol concentration at the same sampling times (with both variables transformed to multiples of the apparent inhibition constant) the discrepancy became even more apparent as time-related counterclockwise hysteresis. None of the known metabolites of penbutolol can explain the discrepancy between the penbutolol concentration and the inhibition of radioligand binding in vitro. It appears that an other active metabolite is formed, which contributes to the effect in vitro and in vivo and so can explain the observed discrepancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637597
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  • 4
    Electronic Resource
    Electronic Resource
    Excretion of azapropazone in human breast milk (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 271-273 
    Details
    ISSN: 1432-1041
    Keywords: azapropazone ; breast feeding ; excretion in milk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The excretion of azapropazone in breast milk was studied in four lactating women over one dosing interval following repeated doses of 600 mg b.d. for at least three days. Plasma and milk samples were collected up to 12 hours after drug intake. An average of 0.8 mg azapropazone was calculated as being excreted in breast milk in the 12 hour period. The breast fed neonate would ingest 0.2 mg/kg during this period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315109
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of torasemide and its metabolites in healthy controls and in chronic renal failure (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 345-348 
    Details
    ISSN: 1432-1041
    Keywords: torasemide ; pharmacokinetics ; metabolites ; chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 20 mg torasemide i.v. has been studied in 7 healthy controls and 9 patients with varying degrees of renal impairment. Torasemide had a t1/2 of about 4 h which was independent of kidney function, as the nonrenal clearance of torasemide was 3-times greater than its renal clearance. The active metabolite M1 and the main metabolite M5 were accumulated in chronic renal failure. In contrast to liver function, therefore, kidney failure does not have an important effect on the pharmacokinetics of torasemide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315407
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  • 6
    Electronic Resource
    Electronic Resource
    The development of reliable compliance tests for antihypertensive drugs (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 535-539 
    Details
    ISSN: 1432-1041
    Keywords: antihypertensive drugs ; compliance tests ; validation ; delay in absorption ; detection interval ; oxprenolol ; hydrochlorothiazide ; pindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Many tests for measuring compliance have been proposed, but in most cases compliance rates have been determined without taking into account the factors influencing the interval during which a drug can be detected by a qualitative test after having been taken by the patient. The drug half-life, often used for determining the time at which the sample is collected, is inadequate for obtaining conclusive test results. A procedure is described for the determination of urine collection intervals during which reliable information on compliance can be obtained, using oxprenolol, hydrochlorothiazide, and pindolol as examples.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635889
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  • 7
    Electronic Resource
    Electronic Resource
    Penbutolol pharmacokinetics: the influence of concomitant administration of cimetidine (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 555-560 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; penbutolol ; pharmacokinetics ; drug metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A possible interaction of penbutolol and cimetidine was investigated in healthy volunteers treated orally for 7 days. The plasma levels of unmetabolised penbutolol showed a slight but non-significant increase. The biphasic elimination kinetics of penbutolol (half-lives 0.8 and 17 h) was not affected by coadministration of cimetidine. Plasma levels of penbutolol were not significantly altered by chronic treatment with cimetidine, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635892
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  • 8
    Electronic Resource
    Electronic Resource
    Concentration of azapropazone in synovial tissues and fluid (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 303-307 
    Details
    ISSN: 1432-1041
    Keywords: azapropazone ; arthritis ; pharmacokinetics ; synovial fluid level ; synovial tissue level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration-time curves of azapropazone in synovial fluid and tissues have been studied in arthritic patients after an i.v. bolus (600 mg) and under steady-state conditions. Synovial fluid and tissue samples were taken intraoperatively 0.45–60 h after administration. The azapropazone concentrations in synovial fluid, synovial tissue and plasma were correlated. The levels in synovial fluid were usually lower than corresponding plasma levels. Under steady-state conditions azapropazone did not accumulate in synovial tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607579
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  • 9
    Electronic Resource
    Electronic Resource
    Single- and multiple-dose pharmacokinetics of R-(−)- and S-(+)-prenylamine in man (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 587-593 
    Details
    ISSN: 1432-1041
    Keywords: prenylamine ; racemic drug ; stereoselectivity ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of S-(+)- and R-(−)-prenylamine was studied in eight healthy volunteers given single and repeated oral doses of the racemic drug. Distinct differences in various pharmacokinetic parameters were found between the S- and R-enantiomer. The maximum plasma concentrations and AUCs of the R-enantiomer exceeded those of the S-enantiomer five-fold; the apparent oral clearance of the S-form was five-times and the renal clearance three-times higher than of the R-form. Acid catalyzed hydrolysis of urine samples released more S-prenylamine, indicating stereoselective glucuronidation of unchanged prenylamine. Plasma protein binding also differed between the two enantiomers, generally with a higher unbound fraction of the S-form, whereas analysis of the bound fractions showed that prenylamine was bound to different plasma proteins with inverse stereoselectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278587
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of amiloride in renal and hepatic disease (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 493-498 
    Details
    ISSN: 1432-1041
    Keywords: amiloride ; pharmacokinetics ; renal failure ; liver disease ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the antikaliuretic amiloride has been studied in healthy controls and in patients with chronic renal failure or hepatitis. It was 40% bound to protein. In healthy volunteers 49% of an oral dose was recovered unchanged in the urine. The renal clearance of amiloride was about 3 times the creatinine clearance, which means that it was predominantly excreted via tubular secretion. Renal impairment reduced the clearance of amiloride, causing a prolongation of the t1/2 and drug accumulation in plasma. In hepatitis the t1/2 of amiloride was prolonged and the AUC increased. Urinary recovery (Ae) of amiloride was greater in hepatitis patients than in controls.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544242
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