PMID- 8842588 OWN - NLM STAT- MEDLINE DCOM- 19961219 LR - 20190826 IS - 0010-7824 (Print) IS - 0010-7824 (Linking) VI - 54 IP - 2 DP - 1996 Aug TI - Effects of two antiprogestins on early pregnancy in the long-tailed macaque (Macaca fascicularis). PG - 107-15 AB - 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. FAU - Tarantal, A F AU - Tarantal AF AD - California Regional Primate Research Center, University of California, Davis 95616, USA. aftarantal@ucdavis.edu FAU - Hendrickx, A G AU - Hendrickx AG FAU - Matlin, S A AU - Matlin SA FAU - Lasley, B L AU - Lasley BL FAU - Gu, Q Q AU - Gu QQ FAU - Thomas, C A AU - Thomas CA FAU - Vince, P M AU - Vince PM FAU - Van Look, P F AU - Van Look PF LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Contraception JT - Contraception JID - 0234361 RN - 0 (Abortifacient Agents, Steroidal) RN - 0 (Norpregnadienes) RN - 0 (Pregnenediones) RN - 0 (Progestins) RN - 320T6RNW1F (Mifepristone) RN - 4G7DS2Q64Y (Progesterone) RN - 6J5J15Q2X8 (ulipristal) SB - IM MH - *Abortifacient Agents, Steroidal MH - *Abortion, Induced MH - Administration, Oral MH - Animals MH - Female MH - Gestational Age MH - Macaca fascicularis MH - *Mifepristone/administration & dosage/adverse effects MH - Norpregnadienes MH - Pregnancy MH - *Pregnenediones/administration & dosage/adverse effects MH - Progesterone/blood MH - Progestins/*antagonists & inhibitors OID - PIP: 115659 OID - POP: 00257116 OAB - The primary objective was to compare the relative potencies of mifepristone and another newly synthesized antiprogestin, HRP 2000 (17-alpha-acetoxy-11-beta-[4-N,N-dimethylaminophenyl]-pregna-4,9- diene-3,20-dione) in terminating early pregnancy in gravid long-tailed macaques. 36 animals were studied with treatment administered either by the oral (0.5 or 5.0 ng/kg; N = 5 per antiprogestin per dose) or intramuscular (im) routes (0.5 ng/kg; N = 5 per antiprogestin) on gestational days (GD) 23-26; 6 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 the 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 the 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 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. OABL- eng OTO - PIP OT - *Abortifacient Agents OT - Abortion, Drug Induced OT - Abortion, Induced OT - Americas OT - *Animals, Laboratory OT - Biology OT - *Clinical Research OT - *Comparative Studies OT - Developed Countries OT - Endocrine System OT - Family Planning OT - Fertility Control, Postconception OT - Hormone Antagonists OT - Hormones OT - North America OT - Northern America OT - Physiology OT - Progestational Hormones OT - *Progesterone OT - Research Methodology OT - *Research Report OT - *Ru-486 OT - Studies OT - United States GN - PIP: TJ: CONTRACEPTION. EDAT- 1996/08/01 00:00 MHDA- 1996/08/01 00:01 CRDT- 1996/08/01 00:00 PHST- 1996/08/01 00:00 [pubmed] PHST- 1996/08/01 00:01 [medline] PHST- 1996/08/01 00:00 [entrez] AID - 0010782496001345 [pii] AID - 10.1016/0010-7824(96)00134-5 [doi] PST - ppublish SO - Contraception. 1996 Aug;54(2):107-15. doi: 10.1016/0010-7824(96)00134-5.