CONCURRENT ADMINISTRATION OF DONEPEZIL HCL AND CIMETIDINE - ASSESSMENT OF PHARMACOKINETIC CHANGES FOLLOWING SINGLE AND MULTIPLE DOSES

Aim The aim of this study was to examine the pharmacokinetics of donep ezil HCl and cimetidine separately, and in combination, following admi nistration of multiple oral doses. Methods This was an open-label, ran domized, 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 bt tween 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 obse rved between the donepezil and the donepezil + cimetidine groups in te rms of the C-max and AUC((0-24)) values for donepezil. The combination group had an 11-13% greater C-max and a 10% greater AUC((0-24)) than the donepezil-only group. No significant difference was observed betwe en die t(max) of the two treatment groups on day 1, and no significant differences in t(max), t(1/2) or the rate of drug accumulation (R-A) 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 cime tidine concentration (C-max) 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-adminis tration of donepezil HCl (5 mg) and cimetidine (800 mg) did not produc e clinically significant changes in the pharmacokinetic profiles of ei ther drug.