Intravenous diltiazem and CYP3A-mediated metabolism
| Autor: | Masica, Andrew L, Azie, Nkechi E, Brater, D Craig, Hall, Stephen D, Jones, David R |
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| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Cross-Over Studies Anticholesteremic Agents Cardiovascular Agents Oxidoreductases N-Demethylating Diltiazem Short Reports Cytochrome P-450 Enzyme System Double-Blind Method Area Under Curve Injections Intravenous Cytochrome P-450 CYP3A Humans Female Aryl Hydrocarbon Hydroxylases Lovastatin Half-Life |
| Popis: | To study whether intravenous diltiazem, a calcium channel blocker commonly prescribed for hypertension and stable angina, is an inhibitor of the CYP3A enzymes by using oral lovastatin, an HMG Co-A reductase inhibitor, as a substrate.Ten healthy volunteers were studied in a randomized two-way crossover design. The two arms were 1) administration of a 20 mg dosage of lovastatin orally and 2) administration of a 20 mg dosage of lovastatin orally 1 h after an intravenous loading dosage and constant infusion of diltiazem. Blood samples were collected up to 25 h in order to quantify lovastatin and diltiazem concentrations in the separated serum. Lovastatin and diltiazem concentrations were quantified by GC-MS and h.p.l.c., respectively.Intravenous diltiazem did not significantly affect the oral AUC, Cmax, t(1/2), or tmax of lovastatin.These data suggest that the interaction of lovastatin with diltiazem does not occur systemically and is primarily a first-pass effect. Thus, drug interactions with diltiazem may become evident when a patient is moved from intravenous to oral dosing. |
| Databáze: | OpenAIRE |
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