Intravenous diltiazem and CYP3A-mediated metabolism.

Author(s): Masica AL, Azie NE, Brater DC, Hall SD, Jones DR

Affiliation(s): Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Wishard Memorial Hospital, OPW 320, 1001 West 10th Street, Indianapolis, IN 46202, USA.

Publication date & source: 2000-09, Br J Clin Pharmacol., 50(3):273-6.

Publication type: Clinical Trial; Randomized Controlled Trial

AIMS: 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. METHODS: 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. RESULTS: Intravenous diltiazem did not significantly affect the oral AUC, Cmax, t(1/2), or tmax of lovastatin. CONCLUSIONS: 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.