Pharmacokinetic evaluation of oral 17 beta-oestradiol and two different fat soluble analogues in ovariectomized women.
A randomised, single-blind comparative study was carried out in 9 ovariectomized women to evaluate the kinetics of single doses of three different steroid combinations: 0.150 mg desogestrel + 2.0 mg micronized 17 beta-oestradiol, 0.150 mg desogestrel + 0.500 mg 17 beta-oestradiol cyclo-octyl acetate and 0.150 mg desogestrel + 1.0 mg 17 beta-oestradiol decanoate. Serum levels of 17 beta-oestradiol and oestrone were measured, as well as the excretion of 17 beta-oestradiol and its metabolites (oestrone and oestriol) in urine. In relation to the doses given, higher peak serum concentrations of 17 beta-oestradiol were obtained after the two fat soluble analogues, while the AUCs were similar to that after micronised 17 beta-oestradiol. However, there was more extensive conversion of the micronised 17 beta-oestradiol preparation into oestrone compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. The oestrone/17 beta-oestradiol serum concentration ratio was approximately 2.6 before tablet intake and remained essentially unchanged after intake of 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate. After micronized 17 beta-oestradiol however, there was a 2-3-fold increase in the ratio at Cmax and slower elimination of 17 beta-oestradiol from plasma, which may be due to the fact that high serum oestrone levels may serve as a reservoir, since both a metabolite and also a precursor of 17 beta-oestradiol. The urinary excretion of 17 beta-oestradiol, oestrone and oestriol was highest after oral administration of micronized 17 beta-oestradiol compared to 17 beta-oestradiol cyclo-octyl acetate and 17 beta-oestradiol decanoate.(ABSTRACT TRUNCATED AT 250 WORDS)
Schubert
W
W
Department of Obstetrics and Gynaecology, University of Göteborg, East Hospital, Sweden.
Cullberg
G
G
Hedner
T
T
D000284:Administration, Oral; D000368:Aged; D017135:Desogestrel / Q000493:pharmacokinetics*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D004964:Estriol / Q000652:urine; D004970:Estrone / Q000652:urine; D005260:Female; D006801:Humans; D008875:Middle Aged; D010052:Ovariectomy; D016037:Single-Blind Method
D004970:Estrone; D004958:Estradiol; C041678:estradiol-17 beta-decanoate; C047085:17-estradiol cyclooctyl acetate; D017135:Desogestrel; D004964:Estriol