Bioequivalence of dienogest as a single component and dienogest in combination with estradiol valerate after single administration to healthy postmenopausal women
H. Zimmermann et al., Bioequivalence of dienogest as a single component and dienogest in combination with estradiol valerate after single administration to healthy postmenopausal women, DRUGS TODAY, 37, 2001, pp. 75-86
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.