Effects of two antiprogestins on early pregnancy in the long-tailed macaque ( Macaca fascicularis)

• Published in: Contraception (Stoneham) 1996-08, Vol.54 (2), p.107-115
• Main Authors: Tarantal, Alice F., Hendrickx, Andrew G., Matlin, Stephen A., Lasley, Bill L., Gu, Quin-Quin, Thomas, Charles A.A., Vince, Pamela M., Van Look, Paul F.A.
• Format: Article
• Language: English
• Subjects: Abortifacient Agents, Steroidal; abortion; Abortion, Induced; Administration, Oral; Animals; Biological and medical sciences; Birth control; Female; Gestational Age; Gynecology. Andrology. Obstetrics; HRP 2000; Induced abortion. Therapeutic abortion; Macaca fascicularis; Medical sciences; mifepristone; Mifepristone - administration & dosage; Mifepristone - adverse effects; monkey; Norpregnadienes; Pregnancy; Pregnenediones - administration & dosage; Pregnenediones - adverse effects; progesterone; Progesterone - blood; Progestins - antagonists & inhibitors; RU 486
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/0010-7824(96)00134-5

The abortifacient effects of mifepristone and HRP 2000 were compared in gravid long-tailed macaques. Thirty-six animals were studied with treatment administered either by the oral (0.5 or 5.0 mg/kg; N = 5 per antiprogestin per dose) or intramuscular (IM) routes (0.5 mg/kg; N = 5 per antiprogestin) on gestational days (GD) 23–26; six vehicle controls were included. Blood samples were collected for assay of progesterone (P 4) and each of the antiprogestins (pre-treatment, daily GD 23–28, every other day GD 30–40), and animals were monitored sonographically throughout gestation. Results of these studies indicated high rates of abortion with IM administration ( 3 5 mifepristone, 4 5 HRP 2000) and 5.0 mg/kg oral route ( 4 5 , 2 5 , respectively), with less effects noted at oral doses of 0.5 mg/kg ( 2 5 , 0 5 , respectively). No early abortions were observed in the control groups. Following daily IM treatment, peak levels of 8–16 ng/ml mifepristone were detected whereas 6–10 ng/ml of HRP 2000 were noted (GD 26–27). No serum levels of mifepristone were detected following either of the oral doses whereas serum levels of 2–6 ng/ml HRP 2000 were noted with high dose oral administration. Results of these studies suggest: (1) both antiprogestins are roughly compatable in terminating early pregnancy although HRP 2000 may be more efficacious when administered IM whereas mifepristone may be more effective when administered rally; (2) similar levels of biological activity are seen with the IM and high dose oral dosing regimens, with little or no activity with the oral low dose; and (3) infants resulting from surviving pregnancies were not affected by early gestation exposure.