Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthyvolunteers

Background: Quercetin is a flavonoid with a wide range of biological activi ties. It mainly occurs in plants as glycosides, such as rutin (quercetin ru tinoside) in tea. Quercetin and rutin are used in many countries as vasopro tectants and are ingredients of numerous multivitamin preparations and herb al remedies. Objectives: The primary objective was to characterise and comp are the absorption and the pharmacokinetics of quercetin from quercetin agl ycone and rutin. A secondary objective was to investigate which forms of qu ercetin are present in plasma. Methods: In this double blind, diet-controlled, two-period cross-over study , 16 healthy volunteers received three different doses of quercetin and rut in orally. The doses corresponded to 8 mg, 20 mg and 50 mg quercetin aglyco ne. Blood samples were obtained between 0 h and 32 h post-dose. Results: The overall kinetic behaviour of quercetin differed remarkably aft er ingestion of quercetin aglycone or rutin. The mean area under the plasma concentration-time curve from 0 h to 32 h [AUC((0-32))] and maximum plasma concentration (C-max) values of the two treatments were similar. However, time to reach C-max (t(max)) was significantly shorter after the quercetin aglycone treatment than after the rutin treatment (1.9, 2.7 and 4.8 versus 6.5, 7.4 and 7.5 h, for doses 1, 2 and 3, respectively). Also, the absorpti on of quercetin from quercetin aglycone was predictable and inter-individua l variation was small. In contrast, after ingestion of rutin, inter-individ ual variations in AUC(0-32) and C-max values were considerable and seemed t o be associated with gender and use of oral contraceptives. Quercetin and r utin were found in plasma as glucuronides and/or sulfates of quercetin and as unconjugated quercetin aglycone, but no rutin was detected. Conclusions: In clinical trials, studying the effects of quercetin from rut in, bioavailability must be taken into consideration and plasma quercetin c oncentrations monitored. Whether our results apply to other glycosidic drug s as well? especially other rutosides, should be investigated.