Effect of food on the bioavailability of gepirone in humans.
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 (t1/2). The mean gepirone Cmax was 16.98 +/- 8.12 ng/mL (fed) and 18.73 +/- 10.30 ng/mL (fasted), with mean t1/2 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, t1/2, or AUCinf. Mean t1/2 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Tay
L K
LK
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Co., Syracuse, New York 13221-4755.
Sciacca
M A
MA
Sostrin
M B
MB
Farmen
R H
RH
Pittman
K A
KA
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002065:Buspirone / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D005215:Fasting / Q000097:blood; D005502:Food; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011743:Pyrimidines; C037921:1-(2-pyrimidinyl)piperazine; C039979:gepirone; D002065:Buspirone