Pharmacokinetic evaluation of gepirone immediate-release capsules and gepirone extended-release tablets in healthy volunteers.
In an open-label, randomized, crossover study, the pharmacokinetics of gepirone immediate-release (gepirone-IR) and different gepirone extended-release (gepirone-ER, types 1, 2, and 3) formulations were compared. Mean maximum concentration (C(max)) was 6.1 ng/mL for gepirone-IR, which was statistically significantly (p < 0.05) higher than that of two of the ER-formulations (3.7 and 3.6 ng/mL, respectively, for types 2 and 3). The mean time to C(max) (mean T(max)) was 1.3 h for gepirone-IR and ranged from 4.8 to 5.6 h for gepirone-ER. The mean area under the curve of concentration versus time (AUC(30)) was similar and not statistically significantly different between gepirone-IR and ER. For the 1-(2-pyrimidinyl)-piperazine (1-PP) metabolite, C(max) and AUC(30) were statistically significantly (p < 0.05) higher and T(max) was lower for gepirone-IR compared with ER. No significant differences in bioavailability were observed between the IR and the three gepirone-ER formulations, indicating that any of the once-daily gepirone-ER formulations could be substituted for gepirone-IR. This study revealed a reduction in the peak-to-trough fluctuations in plasma gepirone concentrations and maintenance of consistent plasma levels with gepirone-ER.
Timmer
C J
CJ
Department of Drug Metabolism and Kinetics, NV Organon, Molenstraat 110, P.O. Box 20, 5340 BH Oss, The Netherlands. cees.timmer@organon.com
Sitsen
J M A
JM
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002065:Buspirone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002214:Capsules; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013997:Time Factors
D002214:Capsules; D003692:Delayed-Action Preparations; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; D013607:Tablets; C037921:1-(2-pyrimidinyl)piperazine; C039979:gepirone; D002065:Buspirone