title: Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert.
abstract: BACKGROUND
  Progesterone vaginal insert (PVI), an effervescent delivery system, dissolves rapidly, is absorbed through the vaginal epithelium, and achieves higher endometrial tissue concentrations than those achieved with progesterone in oil (PIO) given im.
  
  
  OBJECTIVE
  Our objective was to examine the pharmacokinetics and pharmacodynamics of PVI compared with PIO.
  
  
  METHODS
  Fifty-eight healthy premenopausal women were randomized to 50, 100, or 200 mg PVI once daily; 100 or 200 mg PVI twice daily; or 50 to 100 mg PIO via im injection once daily for 10 days. Serum samples were obtained after the first dose; serum and endometrial tissue were obtained after the last dose.
  
  
  METHODS
  Maximum observed serum concentration (Cmax), time to Cmax, and area under the serum-concentration time curve over the dosing interval were calculated after correcting for baseline progesterone concentrations. ANOVA and paired t test were used to compare results across and within groups.
  
  
  RESULTS
  A higher Cmax was observed after PIO than PVI administration. Endometrial tissue progesterone concentrations were higher for PVI regimens. Time to Cmax was 7.3 hours after PIO and 3.3 to 5.9 hours after PVI. Steady state was achieved within 24 and 48 hours for PVI and PIO regimens, respectively. The area under the curve increased with increasing PVI dosage; however, the increase was not proportional to the increase in dosage. Downregulation of estrogen and progesterone receptors was observed in secretory biopsy specimens.
  
  
  CONCLUSIONS
  The PVI system consistently allowed for rapid progesterone absorption and achieved higher endometrial tissue concentrations and lower systemic exposures than observed after im PIO.
authors.affiliation: Keck School of Medicine (R.J.P), University of Southern California, Los Angeles, California 90033; Ferring Pharmaceuticals (M.G.C, V.Y), Parsippany, New Jersey 07054.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Paulson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Collins
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Yankov
mesh_terms: D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D011374:Progesterone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D011374:Progesterone