Drug Interactions with Piperine Major Constituent of Black Pepper

Piperine, a major constituent of black and long pepper, has been reported to act as bioavailability enhancer of several drugs by inhibiting drug metabolism and by increasing oral absorption. Bharadwaj et al. reported that piperine inhibits both the drug transported P-glycoprotein and the major drug metabolizing enzyme CYP3A4. Therefore, dietary piperine could affect plasma concentrations of drugs that are substrates of P-glycoprotein or CYP3A4 enzyme especially if administered orally (138). Animal study using rat model has demonstrated that piperine enhanced bioavailability of beta-lactam antibiotics amoxicilline and cefotaxime (139). Piperine also enhanced the effect of pentobarbital-induced sleeping time in rats due to higher blood and brain levels of pentobarbital in the presence of piperine (140).

Administration of piperine significantly increased plasma rifampicin concentrations in patients with pulmonary tuberculosis (141). Rifampicin is a substrate of P-glycoprotein, and inhibition of P-glycoprotein by piperrine is a possible mechanism. In a study involving six human subjects, piperine (20 mg daily dose) increased both maximum serum concentration and AUC of propranolol. Comparable effects were also observed with theophylline (142). Velpandian et al. reported increased AUC of phenytoin in rats in the presence of piperine. Similar effect was also observed when phenytoin was administered in rats intravenously indicating that piperine also blocked metabolism of phenytoin. Similar effect was also observed with human subjects (143). In another study, 20 mg dose of piperine increased AUC and maximum plasma concentrations of phenytoin compared to controls. The elimination rate constant was also affected (144).

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