THE TEMPORAL EFFECT OF FOOD ON TACRINE BIOAVAILABILITY

A four-way cross-over study was performed to assess the temporal effec t of food on the rate and extent of tacrine (Cognex, THA) absorption a fter drug administration to healthy, older volunteers. Each volunteer received four single 40-mg THA doses at 1-week intervals. Doses were a dministered after an 8-hour overnight fast, 1 hour before a standard b reakfast, 15 minutes after beginning a standard breakfast, and 2 hours after completion of a standard breakfast. Gastrointestinal side effec ts were most frequently reported after drug administration to fasted s ubjects. Mean Cmax and AUC(0-infinity) values after THA administration during breakfast (9.9 ng/mL and 70.2 ng.hr/mL) and 2 hours after brea kfast (11.6 ng/mL and 74.2 ng.hour(-1).mL(-1)) were significantly lowe r than values determined after administration of THA to fasting subjec ts (15.8 ng/mL, and 91.8 ng.hour(-1).mL(-1)). Little effect was eviden t when THA was administered I hour before breakfast.