Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jun 2004
Randomized Controlled Trial Comparative Study Clinical TrialEffect of St John's wort dose and preparations on the pharmacokinetics of digoxin.
St John's wort preparations vary in composition, main constituents, formulation, and daily dose administered. The aim of the study was to evaluate the possible pharmacokinetic interaction of marketed St John's wort formulations and doses with digoxin. ⋯ The interaction of St John's wort and digoxin varies within St John's wort preparations and doses and seems to be correlated with the dose, particularly of hyperforin.
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Clin. Pharmacol. Ther. · Apr 2004
Randomized Controlled Trial Comparative Study Clinical TrialFluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction.
Our objective was to study the effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of tizanidine, a centrally acting skeletal muscle relaxant. ⋯ Fluvoxamine seriously affects the pharmacokinetics of tizanidine and increases the intensity and duration of its effects. Inhibition of tizanidine-metabolizing enzyme(s), mainly CYP1A2, by fluvoxamine seems to explain the observed interaction. Because of the potentially hazardous consequences, the concomitant use of tizanidine with fluvoxamine, or other potent inhibitors of CYP1A2, should be avoided.
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Clin. Pharmacol. Ther. · Mar 2004
Randomized Controlled Trial Comparative Study Clinical TrialSt John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole.
St John's wort, an extract of the medicinal plant Hypericum perforatum, is widely used as an herbal antidepressant. Although the ability of St John's wort to induce cytochrome P450 (CYP) 3A4-mediated reaction has been well established, the effect on CYP2C19 is still not determined. Thus the objective of this study was to determine the impact of St John's wort on the pharmacokinetic profiles of omeprazole and its metabolites. ⋯ St John's wort induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole and enormously decreases the plasma concentrations of omeprazole. Clinically relevant interactions with other drugs may occur and must be taken into account when St John's wort is being taken.
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Clin. Pharmacol. Ther. · Jan 2004
Randomized Controlled Trial Clinical TrialLanreotide effect on splanchnic blood flow in healthy subjects: effect of the rate of infusion.
Somatostatin is a naturally occurring peptide advocated for the management of hemodynamic complications of chronic liver diseases. The route of administration (bolus application or constant infusion) has been a question of debate. ⋯ On the basis of tolerability and hemodynamic effects, an intravenous infusion of lanreotide seems superior to a bolus injection of the same dose.
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Clin. Pharmacol. Ther. · Dec 2003
Randomized Controlled Trial Clinical TrialRole of P-glycoprotein in the intestinal absorption and clinical effects of morphine.
There is considerable and unexplained individual variability in the morphine dose-effect relationship. The efflux pump P-glycoprotein regulates brain access and intestinal absorption of numerous drugs. Morphine is a P-glycoprotein substrate in vitro, and P-glycoprotein affects morphine brain access and pharmacodynamics in animals. However, the role of P-glycoprotein in human morphine disposition and clinical effects is unknown. This investigation tested the hypothesis that plasma concentrations and clinical effects of oral and intravenous morphine are greater after inhibition of intestinal and brain P-glycoprotein, with the P-glycoprotein inhibitor quinidine used as an in vivo probe. ⋯ Quinidine increased the absorption and plasma concentrations of oral morphine, suggesting that intestinal P-glycoprotein affected the absorption, bioavailability, and, hence, clinical effects of oral morphine. However, quinidine had no effect on morphine concentration-effect relationships, suggesting that if quinidine is an effective inhibitor of brain P-glycoprotein then P-glycoprotein did not appear to have a significant effect on brain access of morphine.