Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women

• Published in: Contraception (Stoneham) 2006-11, Vol.74 (5), p.414-418
• Main Authors: Bapst, Jody L., Ermer, James C., Ferron, Geraldine M., Foss, Deborah, Orczyk, Gayle P.
• Format: Article
• Language: English
• Subjects: Adult; Area Under Curve; Benzoxazines - adverse effects; Benzoxazines - blood; Benzoxazines - pharmacokinetics; Benzoxazines - urine; Biological and medical sciences; Birth control; Cervix Mucus - drug effects; Cohort Studies; Contraceptives, Oral - adverse effects; Contraceptives, Oral - blood; Contraceptives, Oral - pharmacokinetics; Contraceptives, Oral - urine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Genital system. Reproduction; Gynecology. Andrology. Obstetrics; Half-Life; Hormonal contraception; Humans; Medical sciences; Oral contraceptive; Pharmacokinetics; Pharmacology. Drug treatments; Progesterone receptor agonist; Pyrroles - adverse effects; Pyrroles - blood; Pyrroles - pharmacokinetics; Pyrroles - urine; Receptors, Progesterone - agonists; Tanaproget
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/j.contraception.2006.06.004

This study aimed to evaluate the pharmacokinetics, pharmacodynamics and safety of the nonsteroidal progesterone receptor agonist, tanaproget. A randomized, double-blind, placebo-controlled, sequential-group study of ascending single doses of tanaproget was conducted in healthy, 25- to 45-year-old women on cycle days 8 to 12. Eight subjects (six active, two placebo) per cohort received a dose of 0.1, 0.3, 1, 3, 7 (±high-fat meal) or 15 mg. The maximum concentration ( C max) of tanaproget occurred approximately 2 to 3 h after administration. The elimination half-life ( t 1/2) ranged from 12 to 30 h, and the oral clearance was approximately 70 L/h. The pharmacokinetics of tanaproget was not noticeably altered with a high-fat meal. All doses of tanaproget decreased cervical mucus scores (using a modified Insler method), indicating poor production and poor quality of cervical mucus. The most frequent treatment-emergent adverse events were vaginal bleeding/spotting, abdominal cramping and vomiting; their incidence was not dose related and most events were mild. Tanaproget was safe and well tolerated, decreased cervical mucus scores and had a pharmacokinetic profile acceptable for use as a once-daily oral contraceptive.