Bioequivalence of dienogest as a single component and dienogest in combination with estradiol valerate after single administration to healthy postmenopausal women

This study was performed to investigate whether coadministration of estradi ol valerate affects the pharmacokinetics of dienogest. It was performed as an open-label, intraindividual comparison of the two treatments administere d at an interval of 1 week. The aim of the study was to show the bioequival ence of 2 mg dienogest given as a single substance (tablet) in comparison t o 2 mg dienogest given in combination with 2 mg estradiol valerate (coated tablet) following a single dose administration. Sixteen healthy postmenopau sal women aged 45-75 years participated in the study. Blood was collected o ver a period of 36 h after each treatment. Dienogest concentrations were de termined by a validated radioimmunoassay and pharmacokinetic parameters of dienogest were calculated model independently. The primary target parameter s for extent and rate of absorption were the area under the curve extrapola ted to infinity (AUC) and C-max. Secondary target parameters were AUC(0-t ( last)), t(max) and t(1/2). AUC and C-max were 522.8 h x ng x ml(-1) and 45. 2 ng/ml after administration of 2 mg dienogest alone and 503.9 h x ng x ml( -1) and 42.2 ng/ml after administration of 2 mg dienogest in combination wi th 2 mg estradiol valerate. The maximum dienogest concentration occurred at 1 h and t(1/2) was 10 h after both treatments. The 90% confidence interval s of the ratio between both treatments calculated for the two primary targe t parameters AUC and Cma were within the limits of acceptance for bioequiva lence. The relative bioavailability of the 2 mg dienogest test formulation compared to the reference formulation of 2 mg dienogest + 2 mg estradiol va lerate was 104%. Therefore, it can be concluded that coadministration of es tradiol valerate does not affect the pharmacokinetics of dienogest. The tes t and reference preparations were well tolerated. No serious or unexpected adverse events were reported. (C) 2001 Prous Science. All rights reserved.