title: Pharmacokinetics and preliminary efficacy of two vaginal gel formulations of ultra-low-dose estriol in postmenopausal women.
abstract: OBJECTIVE
  To investigate the pharmacokinetics, safety and preliminary effectiveness of ultra-low-dose estriol vaginal gel formulations (20 μg/g (T1) and 50 μg/g (T2)) compared to Ovestinon® (estriol 500 μg/0.5 g (R)) and placebo in postmenopausal women.
  
  
  METHODS
  Forty-three volunteers were randomly assigned to received T1, T2, R or placebo once daily for 21 days. Absorption of estriol after single and multiple administration was analyzed. Cytological changes in the vagina, tolerability and safety were also investigated.
  
  
  RESULTS
  Thirty-six women were included in the pharmacokinetic analysis. Systemic absorption was lower with test formulations (AUC0-t: 171.65 ± 80.18 (T1) and 406.75 ± 199.53 (T2) pg/ml × h) than with Ovestinon® (1221.97 ± 549.06 pg/ml × h). Estriol exposure of the test formulations after multiple administration (AUCss: 36.33 ± 30.52 (T1) and 73.71 ± 46.86 (T2) pg/ml × h) was significantly lower than after single-dose administration and not significantly different between them. In contrast, the exposure after repeated administration of Ovestinon® was considerable and not statistically different from levels after single administration. All estriol formulations produced similar improvement in the vaginal maturation value, while placebo showed a small and not significant change. Overall safety and acceptability were good.
  
  
  CONCLUSIONS
  Estriol 20 and 50 μg/g formulations, while showing a comparable capacity for reversing vaginal atrophy, present a highly favorable safety profile, producing a very low systemic absorption of estriol and significantly lower than that of Ovestinon®.
authors.affiliation: a Department of Obstetrics and Gynecology , Hospital Universitario Virgen de la Arrixaca , Murcia , Spain ;
authors.forename: J L
authors.initials: JL
authors.lastname: Delgado
authors.affiliation: b Department of Obstetrics and Gynecology , Hospital Universitario Marqués de Valdecilla , Cantabria , Spain ;
authors.forename: J
authors.initials: J
authors.lastname: Estevez
authors.affiliation: c Cross Research SA , Arzo , Switzerland ;
authors.forename: M
authors.initials: M
authors.lastname: Radicioni
authors.affiliation: c Cross Research SA , Arzo , Switzerland ;
authors.forename: L
authors.initials: L
authors.lastname: Loprete
authors.affiliation: d Italfarmaco SA , Madrid , Spain.
authors.forename: J
authors.initials: J
authors.lastname: Moscoso Del Prado
authors.affiliation: d Italfarmaco SA , Madrid , Spain.
authors.forename: C
authors.initials: C
authors.lastname: Nieto Magro
mesh_terms: D000282:Administration, Intravaginal; D000368:Aged; D001284:Atrophy; D001682:Biological Availability; D004964:Estriol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D005782:Gels; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D014621:Vagina / Q000473:pathology; D014622:Vaginal Creams, Foams, and Jellies / Q000627:therapeutic use; D014623:Vaginal Diseases / Q000188:drug therapy
chemical_list: D005782:Gels; D010919:Placebos; D014622:Vaginal Creams, Foams, and Jellies; D004964:Estriol
keywords: Ovestinon; Vaginal atrophy; estriol; hormone replacement therapy; maturation value; pharmacokinetics; topical