Quercetin, an in vitro inhibitor of CYP3A, does not contribute to the interaction 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 grapefruit juice and nifedipine has been determined in vivo in humans. Eight healthy volunteers were given in random order 10 mg nifedipine orally, either alone or with 200 ml double strength grapefruit juice, or with 400 mg quercetin. The area under the plasma concentration-time curve (AUC) for nifedipine with grapefruit juice (mean 320 ng ml(-1) h) was increased significantly (P < 0.01) compared with the AUC when nifedipine was given alone (mean 218 ng ml(-1) h). The time to peak plasma concentration for nifedipine with grapefruit juice (1.5 h) was also increased (P < 0.05) compared with control (0.5 h) suggesting delayed absorption. Although quercetin delayed the time to peak nifedipine concentration (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 (which contains <10 mg of quercetin 200 ml(-1)) on the metabolism of nifedipine. Oral doses of quercetin, similar to those possible from the ingestion of other fruits such as strawberries, do not produce in vivo inhibition of CYP3A mediated metabolism of nifedipine.
Rashid
J
J
Clinical Pharmacology Group, University of Southampton, Bassett Crescent East, Southampton SO9 3TU, UK.
McKinstry
C
C
Renwick
A G
AG
Dirnhuber
M
M
Waller
D G
DG
George
C F
CF
D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001682:Biological Availability; D002957:Citrus; D051544:Cytochrome P-450 CYP3A; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011794:Quercetin; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D009543:Nifedipine