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The purpose of this study was to investigate the effects of morin, an antioxidant, on the bioavailability of doxorubicin (DOX) in rats. Thus, DOX was administered intravenously (10 mg/kg) or orally (50 mg/kg) with or without oral morin (0.5, 3 and 10 mg/kg). In the presence of morin, the total area under the plasma concentration-time curve (AUC) of DOX was significantly greater than that of the control. In the presence of 3 and 10 mg/kg of morin, the peak concentration ) was significantly higher than that of the control. Consequently, the absolute bioavailability (AB) of DOX in the presence of morin was 3.7-8.3%, which was significantly enhanced compared with those of the control group (2.7%). The relative bioavailability (RB) of DOX was 1.36 to 3.02 times higher than those of the control group. Compared to the intravenous control, the presence of morin increased the AUC of DOX, but was not significantly affected. The enhanced bioavailability of oral DOX by oral morin may be due to the inhibition of both P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A in the intestine and/or liver by morin. This result may suggest that the development of oral DOX combination with morin is feasible, which is more convenient than the i.v. dosage forms. The present study raised the awareness about the potential drug interactions by concomitant use of DOX with morin.
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