QUERCETIN, AN IN-VITRO INHIBITOR OF CYP3A, DOES NOT CONTRIBUTE TO THEINTERACTION BETWEEN NIFEDIPINE AND GRAPEFRUIT JUICE

Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its role in the reported interaction between grap efruit juice and nifedipine has been determined in vivo in humans. Eig ht healthy volunteers were given in random order 10 mg nifedipine oral ly, either alone or with 200 ml double strength grapefruit juice, or w ith 400 mg quercetin. The area under the plasma concentration-time cur ve (AUC) for nifedipine with grapefruit juice (mean 320 ng ml-1 h) was increased significantly (P < 0.01) compared with the AUC when nifedip ine was given alone (mean 218 ng ml-1 h). The time to peak plasma conc entration for nifedipine with grapefruit juice (1.5 h) was also increa sed (P < 0.05) compared with control (0.5 h) suggesting delayed absorp tion. Although quercetin delayed the time to peak nifedipine concentra tion (1.3 h) it did not alter the AUC of either the parent drug (mean 209 ng ml-1 h) or its first-pass metabolite. The results suggest that quercetin does not contribute to the effects of grapefruit juice (whic h contains <10 mg of quercetin 200 ml-1) on the metabolism of nifedipi ne. Oral doses of quercetin, similar to those possible from the ingest ion of other fruits such as strawberries, do not produce in vivo inhib ition of CYP3A mediated metabolism of nifedipine.