COMPARATIVE INVESTIGATION OF THE RELATIVE BIOAVAILABILITY AND PHARMACOKINETICS OF ESTRONE AFTER ORAL-ADMINISTRATION OF ESTERIFIED ESTROGENSAS SUGAR-COATED TABLETS FORMULATION AND AS ORAL SUSPENSION

In a two-way crossover study in 18 young female volunteers aged from 2 2 to 38 years the relative bioavailability and pharmacokinetics of est erified estrogens were investigated after single administration of a s ugar-coated tablet formulation (Femavit(R) 1.25) in comparison to a si ngle dose of an oral suspension. The content of active ingredients was in both cases 1.25 mg esterified estrogens. As marker compound the do minating active compound estrone (GAS 53-16-7) was chosen. Estrone in serum was measured using a validated radioimmuno assay. The administra tion of the test and reference preparation was performed on either day 3-7 of two subsequent menstruation cycles in order to obtain low endo genous hormone levels. The relative bioavailability of estrone from th e test preparation, based on the total AUC (AUC under the baseline + A UC over the baseline), was 99.2 % (90 %-confidence interval 91.8-107.1 %) und therefore fulfilled the bioequivalence criterion. After deduct ion of the baseline-AUG a relative bioavailability of the sugar-coated formulation of 113.9 % was found, with a broad 90 % confidence interv al of 72.5-178.9 %, due to a higher variability. The absolute C-max va lues were similar (255 pg/ml after tablet administration and 279 pg/ml after suspension), bioequivalence also in regard to C-max was proven. The value of t(max) was 4 h for both preparations.