title: Effect of quercetin on CYP3A activity in Chinese healthy participants.
abstract: The aims of this study were to investigate the effect of quercetin on CYP3A activity in vivo. An open, randomized, 2-period crossover experiment was performed in 18 healthy male volunteers. Genotyped data were available from a total of 165 participants. The allelic frequency was 52.5%. Every volunteer ingested orally 500 mg quercetin or placebo once a day for 13 consecutive days. On day 14, a single 7.5-mg midazolam tablet was administrated orally. The plasma concentrations of midazolam and 1-OH-midazolam were determined over 24 hours. The results showed that coadministration of quercetin in CYP3A5*1/*1 and CYP3A5*1/*3 individuals significantly decreased the area under the curve (AUC(0-12 h)) of midazolam (160.88 ± 45.58 ng·h/mL vs 188.07 ± 65.75 ng·h/mL, P < .05), significantly decreased the AUC(0-∞) of midazolam (165.46 ± 47.15 ng·h/mL vs 211.84 ± 75.80 ng·h/mL, P < .01), shortened t(1/2) (2.06 ± 0.51 h vs 2.75 ± 0.89 h, P < .01), and decreased t(max) significantly (0.48 ± 0.36 h vs 1.06 ± 0.69 h, P < .01), respectively. In conclusion, quercetin significantly induced CYP3A activity to substrate midazolam, and the induction was partly related to the CYP3A5 genotype, being more prominent in CYP3A5*1/*1 and CYP3A5*1/*3 individuals.
authors.affiliation: Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Duan
authors.forename: Sai-Ying
authors.initials: SY
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Ouyang
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Mao
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yang
mesh_terms: D000328:Adult; D000483:Alleles; D002681:China; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D019587:Dietary Supplements; D004790:Enzyme Induction; D018565:Food-Drug Interactions; D005787:Gene Frequency; D056726:Genetic Association Studies; D006207:Half-Life; D006801:Humans; D008297:Male; D050216:Metabolic Detoxication, Phase I; D008874:Midazolam / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D011794:Quercetin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D011794:Quercetin; C040081:1-hydroxymethylmidazolam; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam