Pharmacokinetics of the progesterone antagonist 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynyl) estra-4,9-dien-3-one in the rabbit.
Pharmacokinetic characteristics of compound RU 486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynyl)estra-4,9-dien-3-one) were investigated in 6 immature estrogenized female rabbits. A dose of 3.4 mg/kg was administered either intravenously or orally, in both cases together with 3H-RU 486 (13.4 muCi/kg). The concentration of RU 486 was measured in blood plasma following isolation by thin-layer chromatography. The concentration of ether-extractable metabolites was obtained from the difference between the total ether-extractable radioactivity and the radioactivity of the isolated RU 486. Following the i.v. administration it was found that the disposition of RU 486 could be described by a biexponential curve. The half-life of the slow disposition phase of RU 486 was significantly lower (t1/2 = 52 min: P greater than 0.05) than those of RU 486 metabolites (t1/2 = 99 min). High apparent volumes of distribution of RU 486 and RU 486 metabolites (5.8 and 6.0 l/kg, respectively) indicated a high extravascular binding. Following the oral administration in oil solution, RU 486 could not be found in plasma in reliably detectable amounts due to a poor absorption and a probable first-pass effect. In the measurements of the "total RU 486" (sum of RU 486 and ether-extractable metabolites), a similar rate of terminal disposition was found for both routes of administration.
D000818:Animals; D002855:Chromatography, Thin Layer; D004963:Estrenes / Q000097:blood / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D006207:Half-Life; D007700:Kinetics; D015735:Mifepristone; D011817:Rabbits
D004963:Estrenes; D005938:Glucocorticoids; D015735:Mifepristone