Effect of Food on the Bioavailability of Gepirone in Humans

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Abstract
A randomized two‐period crossover study was conducted in 20 healthy male volunteers to assess the effect of food on the pharmacokinetics of gepirone (BMY‐13805) and its metabolite, 1‐(2‐pyrimidinyl)‐piperazine (1‐PP) after a single 20‐mg dose of gepirone either after fasting or after consumption of a standard high‐Fat breakfast. There was a 1‐week washout period between treatments. Plasma samples were obtained predose and at specified time points after dosing and analyzed for gepirone and 1‐PP content by a specific gas chromatographic‐mass spectrometric method. Food did not significantly affect gepirone maximum peak plasma concentration (Cmax) and half‐life (R 1/2). The mean gepirone Cmax was 16.98 ± 8.12 ng/mL (fed) and 18.73 ± 10.30 ng/mL (fasted), with mean t 1/2 of 3.32 ± 1.84 hours (fed) and 2.94 ± 0.90 hours (fasted). Food significantly increased the mean area under the curveinf (AUCinf) from 55.26 ± 35.74 ng.hour/mL (fasted) to 75.69 ± 42.79 ng.hour/mL (fed), and the mean residence timeinf (MRTinf) 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 significantly increased in the presence of food, 2.0 hours, versus 0.75 hours in the absence of food. For 1‐PP, food had no affect on Cmax, t 1/2, or AUCinf. Mean t 1/2 for 1‐PP in the presence and absence of food was 6.06 ± 1.75 and 5.76 ± 1.75 hours, respectively. MRTinf, however, was increased significantly from 9.32 ± 2.68 hours (fasted) to 10.53 ± 2.89 hours (fed). Median tmax for 1‐PP was also significantly increased from 1.25 hours in the absence of food to 3.0 hours with food. The results of this study indicated that the onset and rate of absorption of gepirone were altered in the presence of food. The amount of gepirone reaching the systemic circulation was also increased in the presence of food. Food did not markedly affect peak blood levels of both parent and metabolite, however, or their elimination kinetics.

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