A study of the interactions between donepezil and yokukansan, cimetidine, and ketoconazole in rats
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Donepezil, a drug used for the treatment of Alzheimer's disease, is metabolized mainly by CYP3A4 and CYP2D6 in humans, and its plasma concentration is elevated by coadministration of ketoconazole or cimetidine. Because yokukansan is reported to improve behavioral and psychological symptoms of dementia in Alzheimer's disease, it is likely that yokukansan is prescribed in combination with donepezil. We investigated whether ketoconazole, cimetidine and yokukansan affects the disposition of donepezil in rats.<BR>Ketoconazole (10 mg/kg) or cimetidine (200 mg/kg) was administered intraperitoneally to male Wistar rats. Donepezil hydrochloride (5 mg/kg) was then administered orally, and plasma donepezil concentration was measured by HPLC-UV. The plasma levels of donepezil were higher in the ketoconazole-coadministered group and the cimetidine-coadministered group than in the control group. The areas under the plasma concentration-time curve were also higher in these two groups than in the control group. In contrast, after repeated oral administration of yokukansan extract powder (1 g/kg) once a day for 7 days, plasma donepezil levels following oral administration of donepezil hydrochloride (5 mg/kg) did not differ from those in the control group. These results indicate that ketoconazole or cimetidine coadministered with donepezil elevates plasma donepezil levels in rats, but coadministered yokukansan has no effect on the disposition of donepezil. These results suggest that yokukansan is unlikely to cause pharmacokinetic interactions when coadministered with donepezil in clinical practice.
- 和漢医薬学会の論文
和漢医薬学会 | 論文
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