Effect of pomegranate juice on the pharmacokinetics of nitrendipine in rabbits

Abstract

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.

Interaction of Cyclosporine A with Pomegranate Juice and Its Potential Nephroprotective Effect in Rats

“…In the present study, repeated daily administration of oral pomegranate juice lead to a significant increase in the oral bioavailability of CsA. Similar pharmacokinetic interactions with pomegranate juice were documented with a number of other drugs including carbamazepine [32], nitrendipine [33] and buspirone [34]. In these studies, administration of pomegranate juice in animal models lead to significant increase in the peak plasma concentrations and bioavailability of these drugs.…”

“…This may explains the increase in CsA bioavailability following pomegranate juice administration in our study. Pomegranate juice has also been reported to inhibit the efflux transporter P-gp [33]; leading to increased intestinal permeability of drugs and the fraction of drug absorbed. Moreover, it appears that inhibition of CYP3A4 and P-gp by pomegranate juice is more predominant in the intestine; more so than in the liver [32,33,40,41].…”

“…Pomegranate juice has also been reported to inhibit the efflux transporter P-gp [33]; leading to increased intestinal permeability of drugs and the fraction of drug absorbed. Moreover, it appears that inhibition of CYP3A4 and P-gp by pomegranate juice is more predominant in the intestine; more so than in the liver [32,33,40,41]. Taken together, it is likely that the mechanism underlying the increase in CsA bioavailability in our study following administration of pomegranate juice is probably due to inhibition CYP3A4/5 iso-enzymes and P-gp in the intestine.…”

Pomegranate Juice does not Affect the Bioavailability of Cyclosporine in Healthy Thai Volunteers

“…Pomegranate juice increased the bioavailability of buspirone in rabbits [ 30 ]. Pomegranate juice also significantly increased the area under the concentration-time curve and peak plasma concentration of nitrendipine by 2.03- and 2-fold, respectively, in rabbits [ 31 ].…”

The Challenge and Importance of Integrating Drug–Nutrient–Genome Interactions in Personalized Cardiovascular Healthcare

“…This could at least in part be associated with the effect of grapefruit on the stereoselective metabolism of nicardipine, slightly in favor of (+)-nicardipine compared to (-nicardipine [55]. Scarce evidence on nitrendipine DNGIs in humans suggests an effect of grapefruit on AUC increase, while in vivo animal studies showed an effect of pomegranate juice, a potent CYP3A inhibitor, on intestinal CYP3A4 activity, AUC, and maximal plasma concentration [56][57][58]. Overall, although no official recommendations about these dihydropyridine CCBs and grapefruit or pomegranate interactions are currently available, healthcare professionals should be aware of possible DNGIs and should advise patients to exert caution when consuming grapefruit or pomegranate while on these medications.…”