College of Pharmacy, Chosun Univ., 375 Seo-suk dong, Dong-Gu, Gwangju, Korea.
J Food Sci. 2010 Apr;75(3):H93-6. 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 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.
本研究旨在探讨黑胡椒主要成分胡椒碱对大鼠体内非索非那定口服暴露的影响。在给予大鼠口服（10mg/kg）或静脉注射（5mg/kg）非索非那定的情况下，分别给予胡椒碱（10 或 20mg/kg，口服），确定非索非那定的药代动力学参数。与单独给予非索非那定的对照组相比，联合使用胡椒碱使非索非那定的口服暴露（AUC）增加了 180%至 190%，而大鼠中非索非那定的 C(max)和 T(1/2)没有明显变化。胡椒碱的生物利用度通过联合使用增加了约 2 倍。此外，T(max)趋于增加，这可能归因于胡椒碱存在时胃排空延迟。相比之下，胡椒碱不改变非索非那定的静脉药代动力学，这表明胡椒碱可能主要增加非索非那定的胃肠道吸收，而不是降低肝提取。总之，胡椒碱显著增加了大鼠中非索非那定的口服暴露，可能是通过抑制肠道吸收过程中 P-糖蛋白介导的细胞外排，提示与非索非那定联合使用胡椒碱或含胡椒碱的饮食可能需要密切监测潜在的药物-饮食相互作用。
