EFFECT OF FOOD ON THE BIOAVAILABILITY OF GEPIRONE IN HUMANS

A randomized two-period crossover study was conducted in 20 healthy ma le volunteers to assess the effect of food on the pharmacokinetics of gepirone (BMY-13805) and its metabolite, 142-pyrimidinyl)-piperazine ( 1-PP) after a single 20-mg dose of gepirone either after fasting or af ter consumption of a standard high-fat breakfast. There was a 1-week w ashout period between treatments. Plasma samples were obtained predose and at specified time points after dosing and analyzed for gepirone a nd 1-PP content by a specific gas chromatographic-mass spectrometric m ethod. Food did not significantly affect gepirone maximum peak plasma concentration (Cmax) and half-life (t1/2). The mean gepirone Cmax was 16.98 +/- 8.12 ng/mL (fed) and 18.73 +/- 10.30 ng/mL (fasted), with me an t1/2 of 3.32 +/- 1.84 hours (fed) and 2.94 +/- 0.90 hours (fasted). Food significantly increased the mean area under the curve(inf) (AUC( inf) from 55.26 +/- 35.74 ng.hour/mL (fasted) to 75.69 +/- 42.79 ng.ho ur/mL (fed), and the mean residence time(inf) (MRT(inf)) from 4.31 +/- 0.78 hours (fasted) to 5.37 +/- 1.21 hours (fed). The median time to maximum plasma concentration (tmax) for gepirone was also significantl y increased in the presence of food, 2.0 hours, versus 0.75 hours in t he absence of food. For 1 -PP, food had no affect on Cmax, t1/2, or AU C(inf). Mean t1/2 for 1-PP in the presence and absence of food was 6.0 6 +/- 1.75 and 5.76 +/- 1.75 hours, respectively' MRT(inf), however, w as increased significantly from 9.32 +/- 2.68 hours (fasted) to 10.53 +/- 2.89 hours (fed). Median tmax for 1-PP was also significantly incr eased from 1.2.5 hours in the absence of food to 3.0 hours with food. The results of this study indicated that the onset and rate of absorpt ion of gepirone were altered in the presence of food. The amount of ge pirone reaching the systemic circulation was also increased in the pre sence of food. Food did not markedly affect peak blood levels of both parent and metabolite, however, or their elimination kinetics.