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.

Graphical abstractPlasma concentration–time profiles of talinolol following a single oral dose of 100 mg alone (control), with a single dose of quercetin and after short-term treatment with quercetin (mean ± SD, n = 10).Figure optionsDownload full-size imageDownload high-quality image (98 K)Download as PowerPoint slide