The interaction of diltiazem with simvastatin

Background: Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that is used as a cholesterol-lowering agent and is metabolized by cytochrome P450 3A (CYP3A) enzymes. Diltiazem is a substrate and an inhibitor of CYP3A enzymes and is commonly coadministered with cholesterol-lowering agents such as simvastatin, The objective of this study was to quantify the effect of diltiazem on the pharmacokinetics of simvastatin. Method: A fixed-order study was conducted in 10 healthy volunteers with a 2-week washout period between the phases. In one arm of the study, a single 20-mg dose of simvastatin was administered orally; the second arm entailed administration of a single 20-mg dose of simvastatin orally after 2 weeks of treatment with 120 mg diltiazem twice a day. Results: Diltiazem significantly increased the mean peak serum concentration of simvastatin by 3.6-fold (P < .05) and simvastatin acid by 3.7-fold (P < .05), Diltiazem also significantly increased the area under the serum concentration-time curve of simvastatin fi-fold (P <.05) and the elimination half-life 2.3-fold (P < .05), There was no change in the time to peak concentration for simvastatin and simvastatin acid. Conclusion: Diltiazem coadministration resulted in a significant interaction with simvastatin, probably by inhibiting CYP3A-mediated metabolism, Concomitant use of diltiazem or other potent inhibitors of CYP3A with simvastatin should be avoided, or close clinical monitoring should be used.