title: Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women.
abstract: OBJECTIVE
  Estetrol (E4) is a natural fetal estrogen. In this open-label, multiple-rising-dose study, the pharmacokinetic effects of E4 in postmenopausal women were investigated as a secondary objective.
  
  
  METHODS
  In total, 49 postmenopausal women were randomized to receive either 2 mg E4 or 2 mg estradiol valerate (E2V) for 28 days, or were (non-randomized) assigned to 10, 20, or 40 mg E4. The main outcome measures were: E4 plasma concentrations at trough, and on days 1 and 28; and E4 pharmacokinetic parameters AUC, Cmaxand tmaxon days 1 and 28.
  
  
  RESULTS
  After oral administration, E4 showed a very fast absorption, followed by a multiphasic elimination with an initial rapid decline, gradually continuing with a slower elimination, suggesting a long terminal half-life. Steady state was reached within 2 weeks of dosing and pharmacokinetic results were generally proportional to the dose. Estetrol concentrations on day 28 were slightly higher compared to day 1, indicating some accumulation.
  
  
  CONCLUSIONS
  The pharmacokinetic profile of estetrol is characterized by a very fast absorption phase, followed by an initial rapid decline, and a slow terminal elimination phase. Based on its kinetic properties, estetrol seems suitable for use as a once-daily oral drug.
authors.affiliation: a Pantarhei Bioscience BV , Zeist , The Netherlands.
authors.forename: H J T
authors.initials: HJT
authors.lastname: Coelingh Bennink
authors.affiliation: a Pantarhei Bioscience BV , Zeist , The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Verhoeven
authors.affiliation: a Pantarhei Bioscience BV , Zeist , The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Zimmerman
authors.affiliation: a Pantarhei Bioscience BV , Zeist , The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Visser
authors.affiliation: b Department of Obstetrics and Gynecology , University of Liège , Liège , Belgium.
authors.forename: J-M
authors.initials: JM
authors.lastname: Foidart
authors.affiliation: c Department of Women's and Children's Health , Karolinska Institutet and Karolinska University Hospital , Stockholm , Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Gemzell-Danielsson
mesh_terms: D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D004953:Estetrol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D004953:Estetrol
keywords: Estetrol; menopausal hormone treatment; pharmacokinetics