Human Reproduction, Vol. 15, No. 5, 1100-1106,
May 2000
© 2000 European Society of Human Reproduction and Embryology
Circulating concentrations of the antiprogestins CDB-2914 and mifepristone in the female rhesus monkey following various routes of administration*
1 BIOQUAL, Inc., Rockville, MD, 20850, USA and 2 Contraception and Reproductive Health Branch, National Institute of Child Health and Human Development, Rockville, MD, 20892, USA
The overall aim of these studies was to investigate the oral and i.m. bioavailability of CDB-2914 in intact female rhesus monkeys, and to compare the serum concentrations of CDB-2914 with that of mifepristone following oral administration. In the first study, a 50 mg bolus of CDB-2914 per monkey was administered intravenously, orally or intramuscularly. The area under the serum concentration–time curve for 72 h (AUC0–72) following i.v. injection was 18 320 ± 2718 ng/ml•h, and that for oral administration was 10 464 ± 3248 ng/ml•h. Thus, the oral bioavailability of CDB-2914 equivalents was 56%. The AUC0–168 h following i.m. injection was 11 226 ± 1130 ng/ml•h. Therefore, the i.m. bioavailability of CDB-2914 equivalents was 62%. In the second study, the serum concentrations of CDB-2914 and mifepristone equivalents were compared following an oral bolus dose in two different formulations. When administered at 5 mg/kg in aqueous suspending vehicle (ASV), the mean peak serum concentration (Cmax) of CDB-2914 equivalents (192 ± 64 ng/ml) occurred at 5 ± 1 h, whereas the Cmax of mifepristone equivalents (82 ± 25 ng/ml) occurred at 3 ± 1 h. Following administration in gelatin capsules (35 mg/monkey), the Cmax of CDB-2914 equivalents (129 ± 24 ng/ml) occurred at 5 ± 1 h, while the Cmax of mifepristone equivalents (31 ± 8 ng/ml) occurred at 3 ± 1 h. The serum concentration (AUC0–120 h) of CDB-2914 equivalents was 4.7- or 5.3-fold greater than that of mifepristone equivalents when administered orally in ASV or gelatin capsules respectively. The serum protein binding characteristics of CDB-2914 were also studied. CDB-2914 bound to human 
1-acid glycoprotein (AAG), but not with as high an affinity as mifepristone. In contrast, neither CDB-2914 nor mifepristone bound with high affinity to AAG, corticosteroid binding globulin or sex hormone binding globulin in monkey serum. Collectively, these results indicated that CDB-2914 was more efficiently absorbed than mifepristone following oral administration to female rhesus monkeys.
Key words: antiprogestin/bioavailability/contraception/protein binding/rhesus monkey
3 Present address: Alexion Pharmaceuticals, Inc., New Haven, CT 06511, USA
4 To whom correspondence should be addressed
* Presented in part at the 10th International Congress of Endocrinology, San Francisco, California,1996, Abstract P2-691
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