Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

• Published in: Contraception (Stoneham) Vol. 34; no. 5; pp. 469 - 481
• Main Authors: Swahn, M.L., Wang, G., Aedo, A.R., Cekan, S.Z., Bygdeman, M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.1986
• Subjects: Abortifacient Agents - administration & dosage; Abortifacient Agents - blood; Administration, Oral; Body Burden; Estrenes - administration & dosage; Estrenes - blood; Female; Humans; Kinetics; Mifepristone; Pregnancy; Pregnancy Trimester, First - drug effects; Laboratory Examinations And Diagnoses; Reproductive Control Agents; Biology; Laboratory Procedures; Family Planning; Research Methodology; Examinations And Diagnoses; Endocrine System; Abortion, Induced; Fertility Control, Postconception; Pregnancy; Hormones > analysis; Reproduction; Hormones > administraction and dosage; Data Analysis; Physiology
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/0010-7824(86)90056-9

RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 μmol/1 in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 μmol/1, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of the compound to prevent implantation, induce menstruation or terminate an early pregnancy.