Differences in pharmacokinetics and comparative bioavailability between premarin® and estratab® in healthy postmenopausal women

A single-dose, randomized, two-period, crossover study was conducted to compare the pharmacokinetics and relative bioavailability of the estrogens in Estratab® (esterified estrogens) with those in Premarin® (conjugated estrogens). Twenty-five healthy, postmenopausal women completed both study periods. Plasma concentration versus time profiles of four estrogens were examined over 48 hours using sensitive and specific gas chromatography/mass spectrophotometry/mass spectrophotometry methods. The conjugated and unconjugated estrogens generally showed slow absorption (t_max, 5 to 9 hours), slow elimination (half-life, 10 to 18 hours), and lengthy mean residence times (MRT, 13 to 28 hours). The relative bioavailability (100 · AUC_Estratab/AUC_Premarin) for the estrogens was 146% for total (conjugated plus unconjugated) estrone, 150% for estrone, 36% for total equilin, and 29% for equilin. Differences in peak plasma concentrations (C_max) of the estrogens were similar to the differences seen in the area under the concentration versus time curve (AUC). The time of maximum concentration (t_max) of the estrogens was approximately 1 to 2 hours shorter following Estratab administration. Estratab and Premarin have differences in the rate and extent of both the absorption of estrogens and the formation of the unconjugated metabolites. Thus these two agents cannot be considered bioequivalent, and therapeutic substitution should not be made.