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 per dose) or intramuscular (i.m.) 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 (P4) 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 i.m. 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 i.m. 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 administratation. Results of these studies suggest: (1) both antiprogestins are roughly comparable in terminating early pregnancy although HRP 2000 may be more efficacious when administered i.m. whereas mifepristone may be more effective when administered orally; (2) similar levels of biological activity are seen with the i.m. 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.
Tarantal
A F
AF
California Regional Primate Research Center, University of California, Davis 95616, USA. aftarantal@ucdavis.edu
Hendrickx
A G
AG
Matlin
S A
SA
Lasley
B L
BL
Gu
Q Q
QQ
Thomas
C A
CA
Vince
P M
PM
Van Look
P F
PF
D000021:Abortifacient Agents, Steroidal; D000028:Abortion, Induced; D000284:Administration, Oral; D000818:Animals; D005260:Female; D005865:Gestational Age; D008252:Macaca fascicularis; D015735:Mifepristone / Q000008:administration & dosage / Q000009:adverse effects; D009649:Norpregnadienes; D011247:Pregnancy; D011282:Pregnenediones / Q000008:administration & dosage / Q000009:adverse effects; D011374:Progesterone / Q000097:blood; D011372:Progestins / Q000037:antagonists & inhibitors*
D000021:Abortifacient Agents, Steroidal; D009649:Norpregnadienes; D011282:Pregnenediones; D011372:Progestins; D015735:Mifepristone; D011374:Progesterone; C094854:ulipristal