Carbamazepine markedly reduces serum concentrations of simvastatin and simvastatin acid

Objective. The aim of this study was to examine the effect of carbamazepine on the pharmacokinetics of orally administered simvastatin in healthy volunteers. Methods. In a randomised, two-phase crossover study and a wash out of 2 weeks, 12 healthy volunteers took carbamazepine for 14 days (600 mg daily except 200 mg daily for the first 2 days) or no drug. On day 15, each subject ingested 80 mg simvastatin. Serum concentrations of simvastatin and its active metabolite simvastatin acid were measured up to 24 h. Results. Carbamazepine decreased the mean total area under the serum concentration-time curve of simvastatin and simvastatin acid by 75% (P<0.001) and 82% (P<0.001), respectively. The mean peak concentrations of both simvastatin and simvastatin acid were reduced by 68% (P<0.01), and half-life of simvastatin acid was shortened from 5.9+/-0.3 h to 3.7+/-0.5 h (P<0.01) by carbamazepine. Conclusion. Carbamazepine greatly reduces the serum concentrations of simvastatin and simvastatin acid, probably by inducing their metabolism. Concomitant administration of carbamazepine and simvastatin should be avoided or the dose of simvastatin should be considerably increased.