piperine and fexofenadine

Piperine (PIP) has been found to inhibit P-glycoprotein (P-gp) function in rats, suggesting that it may have the potential to modulate P-gp-mediated drug efflux in humans. The aim of this study was to evaluate the effect of PIP on the pharmacokinetics of fexofenadine (FEX), a P-gp substrate, in healthy volunteers.. An open-label, two-period, sequential study involving 12 healthy volunteers was conducted. A single oral dose of FEX 120 mg was given to volunteers during the control phase and after the treatment phase. A once-daily oral dose of PIP 20 mg was given to volunteers during the treatment phase (10 days). Blood samples were collected at predefined time intervals, and plasma samples containing FEX were analyzed by liquid chromatography-tandem mass spectrometry.. Treatment with PIP significantly increased maximum plasma concentration of FEX [406.9 (control) vs. 767 ng/mL (treatment)] and area under the plasma concentration-time curve [3403.7 (control) vs. 5724.7 ng.h/mL (treatment)] when compared to the control phase. In contrast, PIP treatment significantly decreased apparent oral clearance of FEX [35.4 (control) vs. 20.7 L/h (treatment)] as compared to the control. There was no significant change observed in the half life and renal clearance of FEX between the treatment phase and control phase.. The results suggest that altered pharmacokinetics and enhanced bioavailability of FEX might be attributed to PIP-mediated inhibition of P-gp drug efflux. Therefore, intake of PIP or dietary supplements containing PIP may potentially enhance the absorption or bioavailability of P-gp substrate drugs in addition to FEX.

Topics: Adult; Alkaloids; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzodioxoles; Biological Availability; Half-Life; Healthy Volunteers; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Polyunsaturated Alkamides; Terfenadine

The present study aimed to investigate the effect of piperine, a major component of black pepper, on the oral exposure of fexofenadine in rats. Pharmacokinetic parameters of fexofenadine were determined in rats following an oral (10 mg/kg) or intravenous (5 mg/kg) administration of fexofenadine in the presence and absence of piperine (10 or 20 mg/kg, given orally). Compared to the control group given fexofenadine alone, the combined use of piperine increased the oral exposure (AUC) of fexofenadine by 180% to 190% while there was no significant change in C(max) and T(1/2) of fexofenadine in rats. The bioavailability of fexofenadine was increased by approximately 2-folds via the concomitant use of piperine. Furthermore, T(max) tends to be increased which might be attributed to the delayed gastric emptying in the presence of piperine. In contrast, piperine did not alter the intravenous pharmacokinetics of fexofenadine, implying that piperine may increase mainly the gastrointestinal absorption of fexofenadine rather than reducing hepatic extraction. In conclusion, piperine significantly enhanced the oral exposure of fexofenadine in rats likely by the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal absorption, suggesting that the combined use of piperine or piperine-containing diet with fexofenadine may require close monitoring for potential drug-diet interactions.

Topics: Alkaloids; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzodioxoles; Biological Availability; Chromatography, High Pressure Liquid; Enzyme Inhibitors; Food-Drug Interactions; Gastric Emptying; Half-Life; Histamine H1 Antagonists, Non-Sedating; Intestinal Absorption; Male; Piper nigrum; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Sprague-Dawley; Terfenadine