title: Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin.
abstract: The aim of this study was to investigate the effect of quercetin on the bioavailability of paclitaxel after the oral administration of paclitaxel or a prodrug to rats pretreated with quercetin. Paclitaxel (40 mg/kg) and prodrug (280 mg/kg, 40 mg/kg as the paclitaxel) were administered orally to rats pretreated with quercetin (2, 10, 20 mg/kg). The plasma concentrations of paclitaxel pretreated with quercetin were increased significantly (P < 0.01 for paclitaxel; P < 0.05 for prodrug) compared to the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations (Cmax) of paclitaxel pretreated with quercetin were significantly higher (P < 0.01) than the control. The half-life (t(1/2)) and mean residence times were significantly (P < 0.05) longer compared to the control. The absolute bioavailability (AB%) of paclitaxel pretreated with quercetin was significantly higher (P < 0.01) than the control. The AUC of paclitaxel after administration of the prodrug to rats pretreated with quercetin was significantly (P < 0.05) higher than the prodrug control. The relative bioavailability of paclitaxel after administration of the prodrug to rats pretreated with quercetin was 1.25- to 2.02-fold higher than the prodrug control. The AB% of paclitaxel was increased significantly (P < 0.05) by quercetin from 8.0 to 10.1 and 16.2%. The bioavailability of paclitaxel administered as a prodrug with or without pretreatment of quercetin was remarkably higher than the control. AUC, AB% and Cmax of paclitaxel after administration of the paclitaxel or prodrug pretreated with quercetin for 3 days were much higher than those administered after 20 min. It might have resulted from the physicochemical properties of the prodrug, which is a water-soluble compound and passes through the gastrointestinal mucosa more easily than paclitaxel without obstruction of P-gp and cytochrome P-450 in the gastrointestinal mucosa. It seems that the development of oral paclitaxel preparations as a prodrug or with quercetin is feasible, which is more convenient than the i.v. dosage forms.
authors.affiliation: College of Pharmacy, Chosun University, Gwangju, South Korea. jsachoi@chosun.ac.kr
authors.forename: Jun-Shik
authors.initials: JS
authors.lastname: Choi
authors.forename: Byung-Wok
authors.initials: BW
authors.lastname: Jo
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004357:Drug Synergism; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage*; D011794:Quercetin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011355:Prodrugs; D011794:Quercetin; D017239:Paclitaxel