Single dose pharmacokinetics and bioequivalence of conjugated estrogens (0.625 mg × 2) tablets in healthy post-menopausal female subjects in fasting and fed studies

Abstract Conjugated estrogens are sulfate esters of naturally occurring estrogens. The pharmacokinetics of various estrogen formulations is complex and varying due to its endogenous availability. The present studies were designed to evaluate pharmacokinetic parameters and bioequivalence between two formulations of conjugated estrogens (0.625 mg tablets). Both the studies were designed as two-treatment, four-period, replicate cross-over single dose studies in 60 healthy post-menopausal female subjects under fasting and fed conditions, respectively. Since estrone is present endogenously, for baseline correction three pre-dose samples were obtained for total and unconjugated estrone. Plasma samples were analyzed by validated LC-MS/MS method and pharmacokinetic parameters were estimated for total and unconjugated forms of both estrone and equilin. The least square mean ratios and its 90% confidence interval for primary pharmacokinetic parameters Cmax, AUC0–t and AUC0–inf were found to be within bioequivalence limits of 80.00–125.00% for total and unconjugated forms of baseline corrected estrone and baseline un-corrected equilin. In conclusion, both test and reference products were well-tolerated and the test product was bioequivalent with the reference product in terms of the rate and extent of absorption in both fasting and fed studies.