title: Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment.
abstract: OBJECTIVE
  To investigate the effect of quercetin on organic anion transporting polypeptide 1B1 (OATP1B1) activities in vitro and on the pharmacokinetics of pravastatin, a typical substrate for OATP1B1 in healthy Chinese-Han male subjects.
  
  
  METHODS
  Using human embryonic kidney 293 (HEK293) cells stably expressing OATP1B1, we observed the effect of quercetin on OATP1B1-mediated uptake of estrone-3-sulphate (E3S) and pravastatin. The influence of quercetin on the pharmacokinetics of pravastatin was measured in 16 healthy Chinese-Han male volunteers receiving a single dose of pravastatin (40 mg orally) after co-administration of placebo or 500 mg quercetin capsules (once daily orally for 14 days).
  
  
  RESULTS
  Quercetin competitively inhibited OATP1B1-mediated E3S uptake with a K(i) value of 17.9 ± 4.6 µm and also inhibited OATP1B1-mediated pravastatin uptake in a concentration dependent manner (IC(50) , 15.9 ± 1.4 µm). In healthy Chinese-Han male subjects, quercetin increased the pravastatin area under the plasma concentration - time curve (AUC(0,10 h) and the peak plasma drug concentration (C(max)) to 24% (95% CI 15, 32%, P < 0.001) and 31% (95% CI 20, 42%, P < 0.001), respectively. After administration of quercetin, the elimination half-life (t(1/2) ) of pravastatin was prolonged by 14% (95% CI 4, 24%, P = 0.027), with no change in the time to reach C(max) (t(max) ). Moreover, quercetin decreased the apparent clearance (CL/F) of pravastatin by 18% (95% CI 75, 89%, P < 0.001).
  
  
  CONCLUSIONS
  These findings suggest that quercetin inhibits the OATP1B1-mediated transport of E3S and pravastatin in vitro and also has a modest inhibitory influence on the pharmacokinetics of pravastatin in healthy Chinese-Han male volunteers. The effects of quercetin on other OATP1B1 substrate drugs deserve further investigation.
authors: Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
authors: Lan-Xiang
authors: LX
authors: Wu
authors: Cheng-Xian
authors: CX
authors: Guo
authors: Wang-Qing
authors: WQ
authors: Chen
authors: Jing
authors: J
authors: Yu
authors: Qiang
authors: Q
authors: Qu
authors: Yao
authors: Y
authors: Chen
authors: Zhi-Rong
authors: ZR
authors: Tan
authors: Guo
authors: G
authors: Wang
authors: Lan
authors: L
authors: Fan
authors: Qing
authors: Q
authors: Li
authors: Wei
authors: W
authors: Zhang
authors: Hong-Hao
authors: HH
authors: Zhou
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D019540:Area Under Curve; D044466:Asian People; D002478:Cells, Cultured; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004967:Estrogens / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017035:Pravastatin / Q000493:pharmacokinetics; D011794:Quercetin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D004967:Estrogens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D004970:Estrone; D011794:Quercetin; D017035:Pravastatin; C017296:estrone sulfate