Comparative effectiveness of three antiprogestins alone and in combination with anordiol in terminating pregnancy in the rat

• Published in: Contraception (Stoneham) 1997, Vol.55 (1), p.35-40
• Main Authors: Dao, B., Vanage, G., Li, X.-J., Bardin, C.W., Koide, S.S.
• Format: Article
• Language: English
• Subjects: Abortion, Induced - methods; Administration, Oral; Animals; anordiol; antiprogestins; Biological and medical sciences; Birth control; Cohort Studies; Contraceptives, Postcoital - administration & dosage; Contraceptives, Postcoital - pharmacology; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Estradiol - blood; Estradiol - metabolism; Estrenes - administration & dosage; Estrenes - pharmacology; Female; Furans - administration & dosage; Furans - pharmacology; Gonanes - administration & dosage; Gonanes - pharmacology; Gynecology. Andrology. Obstetrics; Hormone Antagonists - administration & dosage; Hormone Antagonists - pharmacology; Induced abortion. Therapeutic abortion; Male; Medical sciences; mifepristone; Mifepristone - administration & dosage; Mifepristone - pharmacology; Norandrostanes - administration & dosage; Norandrostanes - pharmacology; onapristone; ORG 31806; Pregnancy; pregnancy termination; Progesterone - blood; Progesterone - metabolism; Rats; Rats, Sprague-Dawley
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/S0010-7824(96)00239-9

The effectiveness of mifepristone, onapristone, and ORG 31806 alone or in combination with anordiol to terminate pregnancy in the rat was evaluated. ORG 31806 at a dose of 2 mg/kg/day, mifepristone at 4 mg/kg/day, and onapristone at 8 mg/kg/day, terminated pregnancy in all treated animals. Anordiol, an antiestrogen, at a dose of 5 mg/kg/day, terminated pregnancy in all treated animals. Anordiol acted synergistically with all three antiprogestins terminating pregnancy in the rat. The antiprogestins at doses that were either partially effective or non-effective became 100% effective when administered with a non-effective dose of anordiol. Thus, combination of ORG 31806 (1 mg/kg/day) plus anordiol (0.31 mg/kg/day), mifepristone (1 mg/kg/day) plus anordiol (0.62 mg/kg/day), and onapristone (2 mg/kg/day) plus anordiol (2.5 mg/kg/day) terminated pregnancy in all treated animals. These combinations of the antiprogestins and anordiol decreased significantly the serum progesterone levels but not serum 17β-estradiol levels. The present results indicate that the most potent combination was ORG 31806 plus anordiol.