Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans - Implications for the evaluation of transporter-mediated flavonoid-drug interactions.
Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration-time curve (AUC0-48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7 ng h/ml, p>0.05; 309.7 versus 212.0 and 280.6 ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0-48h was lowered by 23.9% up to 60.6% in 5 subjects and cmax was decreased by 29.2% up to 78.7% in 7 subjects after quercetin co-administration. These effects were less pronounced following repeated quercetin intake. Overlapping modification of efflux and uptake transport involving carrier proteins of the OATP superfamily as well as site-dependent interaction are possible explanations for these observations. In conclusion, clinically relevant quercetin-drug interaction cannot be ruled out.
Institute of Pharmacy, Johannes Gutenberg University, Staudingerweg 5, 55099 Mainz, Germany.
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Nguyen
Department of Dermatology, Clinical Research Center, University Medical Center, Langenbeckstraße 1, 55101 Mainz, Germany.
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Staubach
Institute of Animal Nutrition and Physiology, Christian Albrechts University, Hermann-Rodewald-Straße 9, 24118 Kiel, Germany.
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Wolffram
Institute of Pharmacy, Johannes Gutenberg University, Staudingerweg 5, 55099 Mainz, Germany. Electronic address: P.Langguth@gmx.de.
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Langguth
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D001692:Biological Transport; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011794:Quercetin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
D018435:ATP Binding Cassette Transporter, Subfamily B; D011412:Propanolamines; C011550:talinolol; D011794:Quercetin
Flavonoid; Interaction; OATP; P-glycoprotein; Quercetin; Talinolol