Af. Tarantal et al., EFFECTS OF 2 ANTIPROGESTINS ON EARLY-PREGNANCY IN THE LONG-TAILED MACAQUE (MACACA-FASCICULARIS), Contraception, 54(2), 1996, pp. 107-115
The abortifacient effects of mifepristone and HRP 2000 were compared i
n gravid long-tailed macaques. Thirty-six animals were studied with tr
eatment administered either by the oral (0.5 or 5.0 mg/kg; N = 5 per a
ntiprogestin par dose) or intramuscular (IM) routes (0.5 mg/kg; N = 5
per antiprogestin) on gestational days (GD) 23-26; six vehicle control
s were included. Blood samples were collected for assay of progesteron
e (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) an
d 5.0 mg/kg oral route (4/5, 2/5, respectively), with less effects not
ed at oral doses of 0.5 mg/kg (2/5, 0/5, respectively). No early abort
ions were observed in the control groups. Following daily IM treatment
, peak levels of 8-16 ng/ml mifepristone were detected whereas 6-10 ng
l mi of HRP 2000 were noted (GD 26-27). No serum levels of mifepriston
e were detected following either of the oral doses whereas serum level
s 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 mo
re efficacious when administered IM whereas mifepristone may be more e
ffective when administered orally; (2) similar levels of biological ac
tivity are seen with the IM and high dose oral dosing regimens, with l
ittle or no activity with the oral low dose; and (3) infants resulting
from surviving pregnancies were not affected by early gestation expos
ure.