Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jul 1998
Randomized Controlled Trial Clinical TrialEffect of itraconazole on the pharmacokinetics of atorvastatin.
Itraconazole, a potent inhibitor of CYP3A4, increases the risk of skeletal muscle toxicity of some 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors by increasing their serum concentrations. The aim of this study was to characterize the effect of itraconazole on the pharmacokinetics of atorvastatin, a new HMG-CoA reductase inhibitor that is metabolized at least in part by CYP3A4. ⋯ Itraconazole has a significant interaction with atorvastatin. The mechanism of increased serum concentrations of atorvastatin and HMG-CoA reductase inhibitors is inhibition of CYP3A4-mediated metabolism of atorvastatin and its metabolites by itraconazole. Concomitant use of itraconazole and other potent inhibitors of CYP3A4 with atorvastatin should be avoided or the dose of atorvastatin should be reduced accordingly.
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Clin. Pharmacol. Ther. · Jul 1998
Pharmacokinetics of intravenous dynorphin A(1-13) in opioid-naive and opioid-treated human volunteers.
Dynorphin A(1-13) is a fragment of the endogenous opioid neuropeptide dynorphin A. Previous research suggested that intravenously administered dynorphin A(1-13) has the ability to modulate morphine-induced analgesia. We designed this study to characterize the disposition of intravenous dynorphin immunoreactivity in humans and to determine whether concomitant long-term opioid therapy influenced the pharmacokinetics or side-effects profile of dynorphin A(1-13). ⋯ Intravenously administered dynorphin A(1-13) is very rapidly metabolized, on the basis of the time course of immunoreactivity in the blood. Long-term opioid therapy did not influence either the pharmacokinetics or incidence of side effects.