Open, randomized, crossover study evaluating the relative bioavailability of estradiol valerate and dienogest administered orally as a fixed combination in comparison with a microcrystalline suspension in postmenopausal women

This study was conducted to determine the relative bioavailability of the a ctive ingredients from the coated tablet formulation of Climodien(R) (2 mg estradiol valerate + 2 mg dienogest) and 2 mg estradiol valerate + 3 mg die nogest (EV/DNG 2/3) compared to a microcrystal line suspension. The two tes t preparations were two tablets of Climodien(R) (test 1: 4 mg estradiol val erate + 4 mg dienogest) and two tablets of EV/DNG 2/3 (test 2: 4 mg estradi ol valerate + 6 mg dienogest). The microcrystalline suspension contained 4 mg estradiol valerate and 6 mg dienogest. The three-way crossover design of this study allowed for intraindividual comparison of the concentration res ults for calculation of the relative bioavailability. Nineteen healthy, pos tmenopausal, Caucasian women were recruited and 18 completed the study. Bot h of the test preparations and the reference preparation were well tolerate d by all of the volunteers. The primary target variables were the pharmacok inetic parameters, area under the substance concentration-time curve (AUC) and maximum substance concentration in plasma (C-max), for estradiol and di enogest. For Climodien(R), the estimated relative bioavailability of estrad iol was 101.6% and for dienogest, after dose correction, was 101.4% when co mpared to the microcrystalline suspension. For EV/DNG 2/3, the relative bio availability for estradiol was 98.9% and for dienogest 101.9%. These result s indicate optimal release of the active substances from the coated tablet formulations for both fixed combinations. (C) 2001 Prous Science. All right s reserved.