Cytochrome P450-mediated alterations in clinical pharmacokinetic parameters of conventional drugs coadministered with piperine: a systematic review and meta-analysis

Introduction: Piperine is a main bioactive compound found in Piper nigrum (black pepper) and P. longum (long pepper) and it is a bioenhancer of conventional drugs. The current review is a quantitative synthesis of alterations in the pharmacokinetic parameters of cytochrome (CYP) P450 substrates when coadministered or pretreated with piperine in healthy volunteers. Methods: Electronic databases were searched for randomised-controlled trials on altering the pharmacokinetic activity of conventional drugs with piperine in healthy volunteers, using appropriate search strategies. Percentage mean difference with standard deviation was used to assess the magnitude of difference in the following outcome measures: peak plasma concentration (C_max), time to achieve peak plasma concentration (T_max), half-life (T_1/2), area under the curve zero to infinity (AUC_0-∞) and zero to time t (AUC_0−t), clearance, elimination rate constant, and adverse drug reaction following administration of piperine with conventional CYP substrates. RevMan 5.4.1 software was adopted to evaluate the heterogeneity (I² statistics). Results: A total of 67 studies were identified as per the search strategy, of which five promising studies were included in the present study after the proper abstract screening. The pooled percentage mean difference [95% confidence intervals] showed that there was an increase in the pharmacokinetic parameters of CYP substrates [C_max (P < 0.001), AUC_0‐∞ (P < 0.001), AUC_0−t (P < 0.001), and T_1/2 (P < 0.001)] when administered with piperine. Conclusion: In this review, we concluded that piperine increases the bioavailability of CYP substrates by inhibiting the enzyme CYP. The concurrent use of piperine may provide clinical benefit by enhancing the bioavailability of poorly absorbed CYP substrates.