DIFFERENCES IN PHARMACOKINETICS AND COMPARATIVE BIOAVAILABILITY BETWEEN PREMARIN(R) AND ESTRATAB(R) IN HEALTHY POSTMENOPAUSAL WOMEN

A single-dose, randomized, two-period, crossover study was conducted t o compare the pharmacokinetics and relative bioavailability of the est rogens in Estratab(R) (esterified estrogens) with those in Premarin(R) (conjugated estrogens). Twenty-five healthy, postmenopausal women com pleted both study periods. Plasma concentration versus time profiles o f four estrogens were examined over 48 hours using sensitive and speci fic gas chromatography/mass spectrophotometry/mass spectrephotometry m ethods. The conjugated and unconjugated estrogens generally showed slo w absorption (t(max), 5 to 9 hours), slow elimination (half-life, 10 t o 18 hours), and lengthy mean residence times (MRT, 13 to 28 hours). T he relative bioavailability (100 . AUC(Estratab)/ AUC(Premarin)) for t he estrogens was 146% for total (conjugated plus unconjugated) estrone , 150% for estrone, 36% for total equilin, and 29% for equilin. Differ ences in peak plasma concentrations (C-max) of the estrogens were simi lar to the differences seen in the area under the concentration versus time curve (AUC). The time of maximum concentration (t(max)) of the e strogens was approximately 1 to 2 hours shorter following Estratab adm inistration. Estratab and Premarin have differences in the rate and ex tent of both the absorption of estrogens and the formation of the unco njugated metabolites. Thus these two agents cannot be considered bioeq uivalent, and therapeutic substitution should not be made.