National Facilities in Engineering and Technology with Industrial Collaboration-NAFETIC Centre, University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506009, Andhra Pradesh, India.
Phytother Res. 2012 Aug;26(8):1240-5. doi: 10.1002/ptr.3704. Epub 2012 Jan 25.
Pomegranate juice (PJ) is known to be a potent inhibitor of human cytochromes (CYP), particularly CYP2C9 and CYP3A4. The purpose of this study was to investigate the effect of oral PJ on the pharmacokinetics of nitrendipine (10 mg/kg) in rats. The effect of PJ was also investigated on the absorption kinetics of nitrendipine in rats using a single-pass intestinal perfusion model. There was a significant increase in effective permeability, absorption rate constant and fraction of drug absorbed in the pretreated group when compared with the control group, probably due to inhibition of the P-glycoprotein-mediated efflux of the drug by PJ. In comparison with control, PJ treatment significantly increased the area under the concentration-time curve of oral nitrendipine. The peak plasma concentration of nitrendipine was also significantly increased by PJ. However, elimination half-life of nitrendipine was not altered significantly in both PJ co-administered and pretreated groups. These results suggest that PJ inhibits the intestinal metabolism of nitrendipine without inhibiting the hepatic metabolism in rats. Therefore, the concomitant use of PJ, as food supplement, and nitrendipine should be avoided, although further clinical studies need to be undertaken in order to confirm this finding.
石榴汁（PJ）已知是人类细胞色素（CYP）的有效抑制剂，特别是 CYP2C9 和 CYP3A4。本研究的目的是研究口服 PJ 对大鼠体内硝苯地平（10mg/kg）药代动力学的影响。使用单次肠灌流模型还研究了 PJ 对硝苯地平吸收动力学的影响。与对照组相比，预处理组的有效渗透系数、吸收速率常数和药物吸收分数显著增加，这可能是由于 PJ 抑制了 P-糖蛋白介导的药物外排。与对照组相比，PJ 处理显著增加了口服硝苯地平的 AUC。PJ 还显著增加了硝苯地平的血浆峰浓度。然而，硝苯地平的消除半衰期在 PJ 合用组和预处理组中均无明显改变。这些结果表明，PJ 抑制了硝苯地平在大鼠肠道中的代谢，而不抑制其在肝脏中的代谢。因此，尽管需要进行进一步的临床研究来证实这一发现，但应避免将 PJ 作为食品补充剂与硝苯地平同时使用。
