Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study.
BACKGROUND
Nevirapine is a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase and is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. Piperine (1-piperoylpiperidine) is an alkaloid and the main pungency principle in both black and long pepper. There are indications that piperine inhibits, rather than stimulates, drug metabolism in most cases, thus increasing the bioavailability and effect of some drugs.


METHODS
This was a crossover, placebo-controlled pilot study conducted in a total of eight healthy adult males aged 20-40 years. Subjects were randomly assigned to receive piperine 20mg or placebo each morning for 6 days, and on day 7, nevirapine 200mg plus piperine 20mg or nevirapine plus placebo in a crossover fashion. Blood samples were collected from 1 to 144 hours post-dose for pharmacokinetic analysis.


RESULTS
Mean maximum plasma concentration (C(max)), area under the plasma concentration-time curve from 0 hours to the last measurable concentration (C(last)) [AUC(t)], AUC extrapolated to infinity (AUC(infinity)) and C(last) values of nevirapine were increased by approximately 120%, 167%, 170% and 146%, respectively, when co-administered with piperine. The treatments were well tolerated, indicating few or no clinical adverse effects.


CONCLUSIONS
This pilot study provided evidence for enhanced bioavailability of nevirapine when administered with piperine. Further in-depth studies in a large number of patients receiving different dosage regimens are required to confirm these results and further our understanding of a possible clinical advantage arising from the bioenhancement capabilities of piperine in the treatment of HIV infection.
Kasibhatta
Ravisekhar
R
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.
Naidu
M U R
MU
D000328:Adult; D000470:Alkaloids / Q000009:adverse effects / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D052117:Benzodioxoles / Q000009:adverse effects / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D005215:Fasting; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D019829:Nevirapine / Q000009:adverse effects / Q000493:pharmacokinetics*; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000009:adverse effects / Q000494:pharmacology*
D000470:Alkaloids; D019380:Anti-HIV Agents; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D019829:Nevirapine; C008922:piperine