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

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 par 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 through out 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 ngl mi 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 comparable in terminating early pregnancy although HRP 2000 may be more efficacious when administered IM whereas mifepristone may be more effective when administered orally; (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.