Effects of the flavonol quercetin on the bioavailability of simvastatin in pigs

The influence of the dietary flavonol quercetin on the pharmacokinetics of the HMG-CoA reductase inhibitor simvastatin was investigated in pigs. Simvastatin (0.25 mg/kg body weight) was orally administered to six pigs either without or with quercetin (10 mg/kg). In addition, simvastatin was administered to three pigs that had received a diet supplemented with the flavonol over a period of 1 week. Daily quercetin intake was 10 mg/kg in these animals. Co-ingestion of quercetin with the statin did not alter area under the concentration time curve (AUC0→∞), time to achieve maximum plasma concentration (tmax) or half-life (t1/2) of simvastatin. However, there was a trend towards a reduction of the maximum plasma concentration (Cmax) of simvastatin when quercetin was administered concomitantly (P = 0.06). As compared to controls, AUC0→∞ of simvastatin was significantly decreased after feeding the quercetin-supplemented diet for 1 week. The plasma ratio of simvastatin and its acid metabolite was neither altered by the concomitant quercetin ingestion nor by feeding of the flavonol over a period of 1 week. We conclude that chronic ingestion of high doses of the flavonol quercetin will decrease the bioavailability of simvastatin to a significant extent.