Pharmacokinetics of mifepristone after low oral doses

• Published in: Contraception (Stoneham) 1996-10, Vol.54 (4), p.229-234
• Main Authors: Kekkonen, Raimo, Heikinheimo, Oskari, Mandelin, Erik, Lähteenmäki, Pekka
• Format: Article
• Language: English
• Subjects: Abortifacient Agents, Steroidal - administration & dosage; Abortifacient Agents, Steroidal - blood; Abortifacient Agents, Steroidal - pharmacokinetics; Administration, Oral; Adult; antiprogestin RU 486; Biological and medical sciences; Birth control; Contraceptives, Oral, Synthetic - administration & dosage; Contraceptives, Oral, Synthetic - blood; Contraceptives, Oral, Synthetic - pharmacokinetics; Dose-Response Relationship, Drug; Female; Gynecology. Andrology. Obstetrics; Half-Life; Humans; individual variability; Induced abortion. Therapeutic abortion; Medical sciences; Mifepristone - administration & dosage; Mifepristone - blood; Mifepristone - pharmacokinetics; multiple doses; Population; radioimmunoassay; single dose; Time Factors
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/S0010-7824(96)00193-X

Relatively low doses of the antiprogestin mifepristone (RU 486) have recently proven to be efficient for a variety of possible clinical uses of the drug. However, the pharmacokinetics after low single oral doses have not been characterized. We evaluated the pharmacokinetics of mifepristone following single ingestion of 2 and 25 mg in five women as well as repeated ingestion of 8 mg in two women. Maximal serum concentrations were reached rapidly (within 0.5-2 h) with all doses used. Serum mifepristone concentrations were proportional to the oral doses taken. The mean (±SD) areas under the concentration curves (AUCs) (0–24 h) were 1134 (±144), 4846 (±64), and 17,015 (±4,421) h × ng/mL following 2, 8, and 25 mg doses, respectively. No cumulative increases in serum concentrations were detected with prolonged daily administration of 8 mg of mifepristone. The study subjects appeared to vary in their ability to metabolize mifepristone, as two different half-lives ( t 1 2 ) emerged after both 2 and 25 mg single doses (24.2 ± 0.6 [SD] h for three subjects; and 44.4 ± 1.8 [SD] h for two subjects). We conclude that within the dose range of 2–25 mg/day, the pharmacokinetics of mifepristone are linear, unlike those seen following ingestion of higher daily doses. Keeping in mind previously published data on the biological effects of low dose mifepristone administration, these data infer that certain effects of the drug, such as inhibition of ovulation, might be achieved at serum concentrations of approximately 100 ng/mL.