PubMed | d Italfarmaco SA, Hospital Universitario Marques Of Valdecilla, Hospital Universitario Virgen Of La Arrixaca and c Cross Research SA
Type: Journal Article | Journal: Climacteric : the journal of the International Menopause Society | Year: 2016
To investigate the pharmacokinetics, safety and preliminary effectiveness of ultra-low-dose estriol vaginal gel formulations (20 g/g (T1) and 50 g/g (T2)) compared to Ovestinon (estriol 500 g/0.5 g (R)) and placebo in postmenopausal women.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.Thirty-six women were included in the pharmacokinetic analysis. Systemic absorption was lower with test formulations (AUC0-t: 171.6580.18 (T1) and 406.75199.53 (T2) pg/mlh) than with Ovestinon (1221.97549.06 pg/mlh). Estriol exposure of the test formulations after multiple administration (AUCss: 36.3330.52 (T1) and 73.7146.86 (T2) pg/mlh) 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.Estriol 20 and 50 g/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.