Effects of cranberry juice on nifedipine pharmacokinetics in rats.
Little information is available about drug interactions with cranberry juice (CJ). Using microsomes from the human liver and rat small intestine, this study was designed to determine whether CJ could inhibit CYP3A-mediated nifedipine (NFP) oxidase activity; it showed that CJ was a potent inhibitor of human and rat CYP3A. Preincubation with 10% vol/vol of CJ and 1 mM NADPH for 10 min resulted in significant inhibition of the NFP oxidation activity of human and rat CYP3A (18.2 and 12.6% decreases, respectively, compared with preincubation experiments without NADPH). In addition, the pharmacokinetic interaction between CJ and NFP in vivo was confirmed in rats. In comparison with a control group, the area under the concentration-time curve (AUC) of NFP was approximately 1.6-fold higher when CJ (2 mL) was injected intraduodenally 30 min before the intraduodenal administration of NFP (30 mg kg(-1)). However, the mean residence time, the volume of distribution and the elimination rate constant were not changed significantly. These data suggest that CJ component(s) inhibit the function of enteric CYP3A. In conclusion, it was found that CJ inhibits the CYP3A-mediated metabolism of NFP in both rats and humans. Furthermore, CJ alters NFP pharmacokinetics in rats.
Uesawa
Yoshihiro
Y
Department of Pharmaceutics, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan. uesawa@my-pharm.ac.jp
Mohri
Kiminori
K
D000818:Animals; D001628:Beverages; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D004347:Drug Interactions; D018565:Food-Drug Interactions; D011564:Furocoumarins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009543:Nifedipine / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D029799:Vaccinium macrocarpon
D002121:Calcium Channel Blockers; D011564:Furocoumarins; D009543:Nifedipine