EFFECTS OF QUERCETIN AND MORIN ON THE BIOAVAILABILITY OF DOXORUBICIN IN RATS

Abstract

Doxorubicin (DOX), an anthracycline antibiotic, possesses broad-spectrum antineoplastic activity, and is one of the most important anticancer agents. The purpose of this thesis is to investigate the effects of flavonoids (quercetin and morin) on the bioavailability or pharmacokinetics of DOX in rats. Thus, DOX was administered intravenously (i.v.; 10 mg/kg) or orally (p.o.; 50 mg/kg) without or with oral quercetin (0.5, 3 and 10 mg/kg) or morin (0.5, 3 and 10 mg/kg). In the presence of quercetin (0.5, 3 and 10 mg/kg) and morin (0.5, 3 and 10 mg/kg), the total area under the plasma concentration–time curve from time zero to time infinity (AUC) and the peak plasma concentration (Cmax) of oral DOX were significantly greater and higher, respectively, than those of without flavonoids. Consequently, the extent of absolute oral bioavailability (F) of DOX in the presence of quercetin was considerably greater than that without quercetin. Compared to the i.v. control, the presence of flavonoids increased bioavailability of i.v. DOX. The enhanced bioavailability of oral DOX by oral flavonoids may be due to the inhibition of both P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A subfamily in the intestine and/or liver by flavonoids. This result may suggest that the development of oral DOX combination with flavonoids is feasible, which is more convenient than the i.v. dosage forms. Furthermore, since the present study raised the awareness about the potential drug interactions by concomitant use of DOX with flavonoids (quercetin and morin), the dosage regimen of DOX should be taken into consideration, if this result is confirmed in clinical studies.