A L Masica1, N E Azie, D C Brater, S D Hall, D R Jones. 1. 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.
Abstract
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.
RCT Entities:
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.
Authors: H Y Pan; J Triscari; A R DeVault; S A Smith; D Wang-Iverson; B N Swanson; D A Willard Journal: Br J Clin Pharmacol Date: 1991-06 Impact factor: 4.335