Tiseo_1998_Br.J.Clin.Pharmacol_46 Suppl 1_25

AIM: The aim of this study was to examine the pharmacokinetics of donepezil HCl and cimetidine separately, and in combination, following administration of multiple oral doses.
METHODS: This was an open-label, randomized, three-period crossover study in healthy male volunteers (n=19). During each treatment period, subjects received single daily doses of either donepezil HCl (5 mg), cimetidine (800 mg), or a combination of both drugs for 7 consecutive days. Pharmacokinetic comparisons were made between groups for the day 1 and day 7 profiles. Each treatment period was followed by a 3-week, drug-free washout period.
RESULTS: On both day 1 and day 7, a statistically significant difference was observed between the donepezil and the donepezil + cimetidine groups in terms of the Cmax and AUC(0-24) values for donepezil. The combination group had an 11-13% greater Cmax and a 10% greater AUC(0-24) than the donepezil-only group. No significant difference was observed between the tmax of the two treatment groups on day 1, and no significant differences in tmax, t1/2 or the rate of drug accumulation (RA) were observed between the groups on day 7. Cimetidine pharmacokinetics were essentially unchanged by co-administration of the two drugs. The donepezil + cimetidine treatment group had a 20% greater maximum cimetidine concentration (Cmax) than the cimetidine-only group (P= 0.001) on day 1, but not on day 7, and no difference was observed in any of the other pharmacokinetic parameters examined.
CONCLUSIONS: Co-administration of donepezil HCl (5 mg) and cimetidine (800 mg) did not produce clinically significant changes in the pharmacokinetic profiles of either drug.