Levels of the antiprogestin RU 486 and its metabolites in human blood and follicular fluid following oral administration of a single dose

Using high pressure liquid chromatography (HPLC) the antiprogestin RU 486 and 2 of its metabolites (N-mono-demethyl RU 486 and propargyl RU 486) were measured in plasma and follicular fluid of 21 women requesting laparoscopic sterilization. Pretreatment of the women involved ovulation induction with clomiphene and HCG. RU 486 (100 mg) was administered orally and 1 hour later blood samples were drawn. 34 hours later at laparoscopy samples of both blood and follicular fluid were collected. During the 34 hour period the average plasma level of RU 486 decreased from 1.93 mcmol/1 to 0.91 mcmol/1; i.e. by approximately 50%. The latter concentration of RU 486 was not significantly different from that found in follicular fluid (0.79 mcmol/1). The monodemethyl metabolite exhibited significantly higher plasma levels (3.09 mcmol/1) than RU 486 1 hour after administration. 34 hours later these levels had decreased to 0.92 mcmol/1; i.e. by 70%. In follicular fluid the levels of the monodemethyl metabolite (1.76 mcmol/1) were significantly higher than those of RU 486 (0.79 mcmol/1). Because of background noise only approximate values were established for the propargyl metabolite. These were 0.67 and 0.40 mcmol/1 respectively in plasma and 0.42 mcmol/1 in follicular fluid. The results indicate that RU 486 and 2 of its major metabolites can readily cross the blood-follicle barrier of human preovulatory follicles. (authors)