Pharmacokinetics of a modified-release estrogen tablet.
OBJECTIVE
To determine steady-state plasma concentrations and the pharmacokinetic profile of the essential components of synthetic conjugated estrogens, B (SCE-B), particularly total estrone and delta8,9-dehydroestrone (DHE), after oral administration of a modified-released tablet.


METHODS
A randomized, multiple-dose, pharmacokinetic study of 28 healthy, postmenopausal women randomly assigned to receive two SCE-B 0.3-mg tablets or one 1.25-mg tablet daily for 14 days. Blood samples were obtained before and after dosing at designated times. Total (conjugated and free) and unconjugated estrogens, namely estrone, equilin, and delta8,9-DHE, were determined, and pharmacokinetic analysis was performed.


RESULTS
Steady-state plasma levels of total estrone and total delta8,9-DHE measured on day 14 over a 24-hour period showed minor fluctuations and a similar time to maximum concentration (Tmax): mean Tmax of total estrone = 7.94 and 8.36 hours for 0.3-mg and 1.25-mg tablets, respectively; mean Tmax of total delta8,9-DHE = 7.08 and 8.36 hours for 0.3-mg and 1.25-mg tablets, respectively. Consistency in pharmacokinetic parameters was seen between the two doses of SCE-B.


CONCLUSIONS
SCE-B 0.3-mg and SCE-B 1.25-mg tablets achieved consistent pharmacokinetic parameters and steady-state levels when administered to healthy postmenopausal women. Achieving smooth, predictable levels of component estrogens may result in more consistent relief of menopausal symptoms.
Teva Pharmaceutical Industries, Ltd., Horsham, Pennsylvania, USA. medicalaffairs@barrlabs.com
Rupinder
R
Bhamra
Uwe
U
Kaercher
Christine M
CM
Oleary
D000284:Administration, Oral; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D045166:Estradiol Congeners / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D045166:Estradiol Congeners; D004967:Estrogens; D010936:Plant Extracts; D004970:Estrone; C509657:estrogens, conjugated synthetic B