Article date: May 2012
By: Lan‐Xiang Wu, Cheng‐Xian Guo, Wang‐Qing Chen, Jing Yu, Qiang Qu, Yao Chen, Zhi‐Rong Tan, Guo Wang, Lan Fan, Qing Li, Wei Zhang, Hong‐Hao Zhou, in Volume 73, Issue 5, pages 750-757
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIM
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 Ki value of 17.9 ± 4.6 µm and also inhibited OATP1B1‐mediated pravastatin uptake in a concentration dependent manner (IC50, 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 (Cmax) 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 (t1/2) of pravastatin was prolonged by 14% (95% CI 4, 24%, P = 0.027), with no change in the time to reach Cmax (tmax). 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.
DOI: 10.1111/j.1365-2125.2011.04150.x
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