Clinical pharmacokinetics of tanaproget, a nonsteroidal progesterone receptor (PR) agonist, in healthy cycling women during 28 days of administration

Background Tanaproget is a novel, selective, nonsteroidal PR agonist being studied for contraception. An objective of the study was to characterize the pharmacokinetics of tanaproget after multiple oral doses in healthy cycling women over a range of doses. Methods This multicenter, randomized, double‐blind, sequential‐group ascending multiple‐dose study of tanaproget was conducted in healthy women aged 18 to 35. Once‐daily oral doses of 0.01, 0.03, 0.1, 0.3, and 1 mg of tanaproget were administered for 28 days starting at the beginning of the subject's menstrual cycle in up to 8 subjects per cohort. In each cohort 2 subjects received placebo. Pharmacokinetic profiles were obtained at scheduled intervals after tanaproget administration on days 1, 14, and 28, with trough samples collected on days 7 and 21. Tanaproget plasma concentrations were determined using a validated LC/MS/MS assay. Noncompartmental methods were used to analyze the data. Results Tanaproget was safe and well tolerated. Tanaproget was absorbed rapidly and dose proportionality was observed for the exposure parameters C max and AUC. On day 14, near the time of ovulation, at the predicted therapeutic dose (0.3 mg), C max and AUC were 663 pg/mL and 3327 pg‐h/mL, respectively. The mean elimination t 1/2 was 16 hours, and drug accumulation was modest. Conclusions Tanaproget has an acceptable safety and pharmacokinetic profile for a once‐daily oral contraceptive. Clinical Pharmacology & Therapeutics (2005) 77 , P44–P44; doi: 10.1016/j.clpt.2004.12.060