Effect of pomegranate juice on the pharmacokinetics of nitrendipine in rabbits

Pomegranate juice (PJ) is known to be a potent inhibitor of human cytochrome enzymes. The purpose of this study was to investigate the effect of acute and chronic PJ on the pharmacokinetics of oral nitrendipine (10 mg/kg) in rabbits. Male New Zealand rabbits were pretreated with PJ for 1 week and on the last day, a single dose of nitrendipine was given orally. In another group, both PJ and nitrendipine were co-administered to evaluate the acute effect of PJ on nitrendipine pharmacokinetics. The control group received oral distilled water for 1 week and administered with nitrendipine on the last day. Blood samples were collected at different time points and nitrendipine concentration was estimated by high-performance liquid chromatography. Relative to control, the area under the concentration-time curve and peak plasma concentration of nitrendipine were 2.03- and 2-fold, respectively, greater in the PJ-pretreated group. However, co-administration of PJ had no significant effect on these parameters. Further, there was no significant change in the elimination rate constant and elimination half-life of nitrendipine in both PJ co-administered and pretreated groups in comparison with control. These results suggest that PJ inhibits the intestinal metabolism of nitrendipine without affecting hepatic metabolism in rabbits. Although this potential interaction needs to be explored further, the concomitant use of PJ and nitrendipine should be avoided.