Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women.
OBJECTIVE
This study aimed to evaluate the pharmacokinetics, pharmacodynamics and safety of the nonsteroidal progesterone receptor agonist, tanaproget.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Tanaproget was safe and well tolerated, decreased cervical mucus scores and had a pharmacokinetic profile acceptable for use as a once-daily oral contraceptive.
Bapst
Jody L
JL
Wyeth Research, Collegeville, PA 19426, USA. bapstj@wyeth.com
Ermer
James C
JC
Ferron
Geraldine M
GM
Foss
Deborah
D
Orczyk
Gayle P
GP
D000328:Adult; D019540:Area Under Curve; D048588:Benzoxazines / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002582:Cervix Mucus / Q000187:drug effects; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D011758:Pyrroles / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011980:Receptors, Progesterone / Q000819:agonists*
D048588:Benzoxazines; D003276:Contraceptives, Oral; D011758:Pyrroles; D011980:Receptors, Progesterone; C503890:tanoproget