THE EFFECT OF FOOD ON THE BIOAVAILABILITY OF DOLASETRON MESYLATE TABLETS

Anzemet(R) (dolasetron mesylate) is being developed for the prevention of chemotherapy-induced emesis and postoperative nausea and vomiting. Twenty-four healthy male subjects were orally dosed with dolasetron m esylate, 200 mg, after either an overnight fast or a high-fat breakfas t. The ratio of the mean area under the plasma concentration-time curv e of the reduced active metabolite (MDL 74 156) to infinity (AUC(0-inf inity)) values in fed compared to fasting subjects was 86.3% with a 90 % confidence interval for the ratio within (80, 125)%, indicating bioe quivalence. The ratio of the mean MDL 74 156 maximum plasma concentrat ion (C-max) values was 70.6% in fed versus fasted subjects. The time t o C-max was statistically significantly longer after the high-fat brea kfast (mean values, 1.11 h fasting and 1.80 h fed), probably due to de layed gastric emptying. It may be concluded that, although the rate of absorption was somewhat delayed, the extent of absorption did not cha nge significantly when dolasetron mesylate was given with food. (C) 19 98 John Wiley & Sons, Ltd.