Abstract: Donepezil, an acetylcholinesterase inhibitor, is mainly used for treatment of dementia. Recently, the combination therapy with donepezil has been interested to enhance the efficacy and reduce the potential side effects. Gwibi-Chongmyungtang (GCMT) is one of the most famous Korean medicines used for improving learning and memory. Therefore, pharmacokinetic interactions between donepezil and GCMT were examined for the combination therapy. Rats received oral coadministration of donepezil with GCMT (combination) or donepezil with distilled water (control). The distilled water or GCMT was coadministered by single dosing within 5 min after donepezil or by repeated dosing for a week at 1.5 h intervals. The plasma samples were analyzed for the donepezil concentration and the pharmacokinetic parameters (Tmax, Cmax, AUC, t1/2 and MRTinf). In the single oral coadministration with GCMT within 5 min after donepezil, the combination resulted in reduced plasma concentration of donepezil compared to control, suggesting pharmacokinetic interactions between donepezil and GCMT. There were no differences in the plasma concentration between the combination and control, when GCMT was coadministered at 1.5 h intervals. However, the repeated dosing of combination for a week at 1.5 h intervals decreased plasma concentration of donepezil compared to control. Pharmacokinetic analyses showed reduced AUC0-t and AUC0-inf in the single dosing of combination within 5 min and repeated dosing of combination for a week at 1.5 h intervals, suggesting that GCMT can reduce the bioavailability of donepezil. The current results showed that GCMT is hard to use in combination with donepezil by coadministration within short interval, 5 min or a week repeated dosing despites at 1.5 h intervals.