Intravenous diltiazem and CYP3A-mediated metabolism

Aims To study whether intravenous diltiazem, a calcium channel blocker comm only prescribed for hypertension and stable angina, is an inhibitor of the CYP3A enzymes by using oral lovastatin, an HMG Go-A reductase inhibitor, as a substrate. Methods Ten healthy volunteers were studied in a randomized two-way crossov er design. The two arms were 1) administration of a 20 mg dosage of lovasta tin orally and 2) administration of a 20 mg dosage of lovastatin orally 1 h after an intravenous loading dosage and constant infusion of diltiazem. Bl ood samples were collected up to 25 h in order to quantify lovastatin and d iltiazem concentrations in the separated serum. Lovastatin and diltiazem co ncentrations were quantified by GC-MS and h.p.l.c., respectively. Results Intravenous diltiazem did not significantly affect the oral AUC, C- max, t(1/2), or t(max) of lovastatin. Conclusions These data suggest that the interaction of lovastatin with dilt iazem does not occur systemically and is primarily a first-pass effect. Thu s, drug interactions with diltiazem may become evident when a patient is mo ved from intravenous to oral dosing.