Effect of Piperine, a Major Component of Black Pepper, on the Intestinal Absorption of Fexofenadine and Its Implication on Food-Drug Interaction

• Published in: Journal of food science 2010-04, Vol.75 (3), p.H93-H96
• Main Authors: Jin, Ming-Ji, Han, Hyo-Kyung
• Format: Article
• Language: English
• Subjects: absorption; alkaloids; Alkaloids - pharmacology; animal models; Animals; antihistamines; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; Benzodioxoles - pharmacology; bioavailability; Biological and medical sciences; Biological Availability; black pepper; chemical interactions; Chromatography, High Pressure Liquid; Comparative analysis; diet; Effects; Enzyme Inhibitors - pharmacology; fexofenadine; Food industries; Food science; food-drug interaction; Food-Drug Interactions; Fundamental and applied biological sciences. Psychology; gastric emptying; Gastric Emptying - drug effects; Glycoproteins; Half-Life; Histamine H1 Antagonists, Non-Sedating - administration & dosage; Histamine H1 Antagonists, Non-Sedating - blood; Histamine H1 Antagonists, Non-Sedating - pharmacokinetics; human nutrition; intestinal absorption; Intestinal Absorption - drug effects; Male; oral administration; P-glycoprotein; pharmacokinetics; Piper nigrum - chemistry; Piperidines - pharmacology; piperine; Polyunsaturated Alkamides - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Terfenadine - administration & dosage; Terfenadine - analogs & derivatives; Terfenadine - blood; Terfenadine - pharmacokinetics
• ISSN: 0022-1147; 1750-3841
• DOI: 10.1111/j.1750-3841.2010.01542.x

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 Cmax and T₁/₂ of fexofenadine in rats. The bioavailability of fexofenadine was increased by approximately 2-folds via the concomitant use of piperine. Furthermore, Tmax 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.