Intravenous diltiazem and CYP3A-mediated metabolism

Br J Clin Pharmacol. 2000 Sep;50(3):273-6. doi: 10.1046/j.1365-2125.2000.00249.x.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anticholesteremic Agents / pharmacokinetics
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases*
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / blood
  • Cardiovascular Agents / pharmacology*
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Diltiazem / administration & dosage
  • Diltiazem / blood
  • Diltiazem / pharmacology*
  • Double-Blind Method
  • Female
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Lovastatin / pharmacokinetics
  • Male
  • Oxidoreductases, N-Demethylating / metabolism*

Substances

  • Anticholesteremic Agents
  • Cardiovascular Agents
  • Cytochrome P-450 Enzyme System
  • Lovastatin
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • Diltiazem