The site of gastrointestinal absorption of gepirone in humans.
This study was conducted in seven healthy male subjects and was performed over four sessions with a 1-week washout between sessions. It was designed to compare the bioavailability of an oral 20-mg gepirone dose (treatment 1) with that obtained after application of the same dose by gastric intubation to the distal (treatment 2) and proximal (treatment 3) regions of the small intestine, and after 4 consecutive 5-mg gepirone doses given orally at hourly intervals (treatment 4). Serial blood samples were taken over 24 hours after dose after each treatment. Plasma concentrations of gepirone and 1-(2-pyrimidinyl)-piperazine (1-PP), a metabolite of gepirone, were quantitated by gas chromatography-mass spectrometry. Mean gepirone time to reach peak concentration (tmax) after treatments 1, 2, and 3 ranged between 0.57 and 1.07 hours. There were no significant differences between sites and treatments for gepirone t1/2, which ranged between 2.8 and 3.3 hours. The mean gepirone maximum peak plasma concentration (Cmax) was significantly higher (P less than .05) after treatment 2 (12.92 +/- 7.24 ng/mL) compared with treatment 1 (6.79 +/- 3.54 ng/mL) or treatment 3 (6.33 +/- 2.26 ng/mL). Gepirone area under the curve (AUCinf) was also significantly higher (P less than .05) after treatment 2 (29.83 +/- 17.42 ng.h/mL) compared with treatment 1 (18.07 +/- 6.10 ng.h/mL) or treatment 3 (17.74 +/- 7.69 ng.h/mL). There were no significant differences in gepirone AUCinf between treatments 1 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Syracuse, NY 13221-4755.
L K
LK
Tay
F
F
Dixon
M B
MB
Sostrin
W H
WH
Barr
R H
RH
Farmen
K A
KA
Pittman
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D006801:Humans; D007408:Intestinal Absorption; D007441:Intubation, Gastrointestinal; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; C039979:gepirone