Short-term effect of quercetin on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein, in healthy volunteers.
OBJECTIVE
The aim of the present study was to assess whether quercetin exhibited any inhibitory effect on P-glycoprotein (P-gp)-mediated drug disposition in humans using fexofenadine as a P-gp substrate.


METHODS
Twelve healthy subjects were enrolled in the study and treated daily for 7 days with 500 mg quercetin or placebo 3 times a day. On day 7, a single dose of 60 mg fexofenadine was administered orally. Plasma and urinary fexofenadine concentrations were measured, and pharmacokinetic differences between placebo and quercetin phases were assessed.


RESULTS
The mean plasma concentrations of fexofenadine were significantly increased after quercetin treatment compared to those of the placebo phase. The area under the time versus concentration curve (AUC) of plasma fexofenadine was increased by 55% by quercetin (2,005.3 versus 3,098.6 ng.h/mL, P < 0.001) and similarly the maximum plasma concentration (C(max)) during the quercetin phase was elevated by 68% compared to that of the placebo phase (295.3 versus 480.3 ng/mL, P = 0.006). Although the oral clearance of fexofenadine was decreased significantly by 37% after quercetin treatment (61.4 versus 38.7 L/h, P < 0.001), no differences in the renal clearance and half-life were observed between placebo and quercetin phases.


CONCLUSIONS
The results of the present study showed that short-term use of quercetin elevated the plasma concentrations of fexofenadine, probably by the inhibition of P-gp-mediated efflux in humans.
Kim
Kyoung-Ah
KA
Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Sungbuk-gu, Seoul 136-705, Korea.
Park
Pil-Whan
PW
Park
Ji-Young
JY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D039563:Histamine H1 Antagonists, Non-Sedating / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011794:Quercetin / Q000494:pharmacology*; D012016:Reference Values; D013050:Spectrometry, Fluorescence; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D039563:Histamine H1 Antagonists, Non-Sedating; D016593:Terfenadine; D011794:Quercetin; C093230:fexofenadine