The Site of Gastrointestinal Absorption of Gepirone in Humans

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Abstract
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‐pyrimidiriyl)‐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 < .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 < .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. For 1‐PP, treatment 2 Cmax (19.25 ± 6.64 ng/mL) was significantly higher (P < .05) compared with treatment 1 (13.55 ± 3.26 ng/mL), but not treatment 3 (15.56 ± 4.31 ng/mL). Significant differences were not observed between sites and treatments with respect to 1‐PP t1/2 and AUCinf. Mean 1‐PP t1/2 values ranged between 4.85 and 6.73 hours, and mean tmax between 0.82 and 1.29 hours. These results suggest that even though gepirone may be more bioavailable in the lower regions of the small intestine, gepirone is absorbed throughout the entire length of the small intestine. In addition, differences were not observed in gepirone AUCinf between treatments 1 and 4, suggesting that the bioavailability of gepirone was not affected by changes in the rate of oral administration.

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