Protein binding of active ingredients and comparison of serum ethinyl estradiol, sex hormone-binding globulin, corticosteroid-binding globulin, and cortisol levels in women using a combination of gestodene/ethinyl estradiol (Femovan) or a combination of desogestrel/ethinyl estradiol (Marvelon) and single-dose ethinyl estradiol bioequivalence from both oral contraceptives.
Results from two clinical pharmacokinetic studies are given. The first study was an observational study in oral contraceptive users who took either a combination of gestodene and ethinyl estradiol (pill A, Femovan) or desogestrel and ethinyl estradiol (pill B, Marvelon). A total of 69 women (39 receiving pill A and 30 receiving pill B) were evaluated to determine serum ethinyl estradiol, sex hormone-binding globulin, corticosteroid-binding globulin, and cortisol levels. Samples were obtained on 1 day during the tenth to twenty-first days of pill intake. All women received the respective oral contraceptive for at least 3 months. The test power was such that an 80% difference of 1 standard deviation of each target variable would have been detected (alpha = 0.05; beta = 0.1). No statistically significant differences were found in sex hormone-binding globulin, corticosteroid-binding globulin, or cortisol serum levels between both groups. Time and height of maximum ethinyl estradiol levels were identical as was the area under the curves. Ex vivo protein-binding analysis of the progestins revealed a free portion of 0.6% for gestodene and 2.5% for 3-ketodesogestrel as the active metabolite of desogestrel. Sex hormone-binding globulin-bound portions were much higher for gestodene (75.3% +/- 9.1%) than for 3-ketodesogestrel (31.6% +/- 12%). The remaining fractions were bound to albumin. In a second study, ethinyl estradiol-bioequivalence from pills A and B was investigated in 18 women in a controlled, single-dose, randomized, crossover design. The area under the ethinyl estradiol serum levels were identical up to 4 hours after pill intake between both treatments. According to the relatively low variation in data in this group of women, a 10% difference in ethinyl estradiol-availability could have been detected. Both studies indicate that the pharmacokinetics of ethinyl estradiol were independent of the concomitantly administered progestin, that is, desogestel and gestodene.
Hümpel
M
M
Research Laboratories of Schering AG, Berlin, West Germany.
Täuber
U
U
Kuhnz
W
W
Pfeffer
M
M
Brill
K
K
Heithecker
R
R
Louton
T
T
Steinberg
B
B
Seifert
W
W
Schütt
B
B
D000328:Adult; D001682:Biological Availability; D003277:Contraceptives, Oral, Combined / Q000097:blood* / Q000493:pharmacokinetics; D003278:Contraceptives, Oral, Hormonal / Q000097:blood* / Q000493:pharmacokinetics; D017135:Desogestrel; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D009652:Norpregnenes / Q000097:blood / Q000493:pharmacokinetics; D045167:Progesterone Congeners / Q000097:blood / Q000493:pharmacokinetics; D011485:Protein Binding; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D014156:Transcortin / Q000378:metabolism*
D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D009652:Norpregnenes; D045167:Progesterone Congeners; D012738:Sex Hormone-Binding Globulin; C033273:Gestodene; D004997:Ethinyl Estradiol; D017135:Desogestrel; D014156:Transcortin; D006854:Hydrocortisone