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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., (Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association)

Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from contraceptive vaginal rings (CVRs) with different release rates (75/15, 100/15 and 150/15 micrograms 3-keto-desogestrel/ethinylestradiol daily) were investigated in two studies in young healthy female volunteers. As reference, an oral preparation containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol (MarvelonR tablets) was also administered to the volunteers. To assess the disposition parameters of 3-keto-desogestrel and ethinylestradiol, some of the volunteers were additionally given an i.v. preparation containing 150 micrograms 3-keto-desogestrel and 30 micrograms ethinylestradiol. Serum levels obtained with CVRs showed an initial increase during the first three days, followed by a plateau decreasing only slightly during the remainder of the treatment period. Mean plateau levels (+/- s.d.) of 3-keto-desogestrel were 2.3 +/- 0.9, 2.8 +/- 1.1 and 3.8 +/- 1.1 pmol/ml for CVR 75/15, 100/15 and 150/15, respectively. Mean plateau levels of ethinylestradiol were 184 +/- 75, 262 +/- 102 and 233 +/- 102 pmol/l, respectively. The in vivo release rates of 3-keto-desogestrel and ethinylestradiol from the CVRs were in good agreement with the in vitro release rates. For both steroids the bioavailability from the CVRs was approximately 1.2 times higher than that from the tablets. The 3-keto-desogestrel serum levels were found directly proportional to the release rates within the range studied (75-150 micrograms/day). For ethinylesteradiol the intra-individual variation in steady-state levels was too large to draw pertinent conclusions.