Lovastatin is a HMG CoA reductase inhibitor (HMG-CoA RI) that is eliminated by CYP3A mediated metabolism. Diltiazem is a calcium channel blocker that inhibits CYP3A and is often used concurrently with HMG-CoA RIs. The effect of IV or oral steady state diltiazem on CYP3A, as measured by lovastatin pharmacokinetics, was therefore studied in 10 healthy volunteers. Diltiazem was administered as an IV infusion over 12 h or 120 mg orally b.i.d. for two weeks. Lovastatin (20 mg) was administered before and 1 hour after the infusion or an hour after the final oral dose of diltiazem. Steady-state diltiazem serum concentrations ranged between 0.2-1.2 μM from 1-12 hours after the start of the infusion. IV diltiazem had no significant effect on lovastatin AUC0-24hr, Cmax, and tmax compared to the control treatment. Steadystate serum concentrations of diltiazem after oral administration ranged from 0.2-0.7 μM. Oral diltiazem significantly increased the lovastatin AUC0-24hr and Cmax approximately 4-fold without affecting the t1/2. The lack of effect of IV infusion suggests that diltiazem does not inhibit CYP3A systemically. The influence of diltiazem on lovastatin pharmacokinetics is consistent with an interaction that is restricted to presystemic inhibition of CYP3A in the intestinal wall.
ASJC Scopus subject areas
- Pharmacology (medical)