Effect of Herbal Bio-enhancer (Piperine) on the Bioavailability and Pharmacokinetic of Simvastatin in Wistar rats.

Abstract

Simvastatin is a well-known lipid lowering drug. Because of its extensive presystemic metabolism, CYP3A4 exhibits low oral bioavailability. Piperine, an alkaloid isolated from black and long pepper, is known to inhibit CYP3A4 and therefore it is expected to improve the bioavailability of simvastatin. Based on this assumption, a pharmacokinetic study of simvastatin (10 mg/kg) alone and in combination with piperine (20 mg/kg) was performed in fasted Wistar rats on days 1 and 7 of repeat oral dose administration. Blood sampling was done at different time points up to 24 hours, and the plasma samples collected were analyzed on LC-MS/MS for the estimation of simvastatin. When given together with piperine, the plasma Cmax and AUC of simvastatin was 0.9 ng/mL and 11.4 ng·h/mL on day 1 and 21.6 ng/mL and 57.8 ng·h/mL on day 7, respectively. This Cmax and AUC were 1.4- and 2.9-fold higher on day 1 and 6.4- and 4.7-fold higher on day 7, respectively, compared to simvastatin alone. In the current study, piperine was found to significantly enhance the circulating levels of simvastatin. Therapeutically this interaction could be beneficial in terms of improving the efficacy and can have implication on toxicity. A clinical study can further help to investigate these aspects