Pharmacokinetics and protein binding of gestodene under treatment with a low-dose combination oral contraceptive for three months.
The serum concentrations of gestodene (CAS 60282-87-3) as well as the binding of this progestin to serum proteins were studied in 40 women who took a low-dose oral contraceptive (Femovan, Femodene) containing 30 micrograms ethinyl estradiol (CAS 57-63-6) and 75 micrograms gestodene for 3 months. On days 1, 10, and 21 of the first and the third treatment cycle, respectively, 7 blood samples were drawn before and up to 4 h after pill intake; additional samples were taken prior to morning ingestion of pill on days 2, 5, 11, 15 and 22 of these cycles. Gestodene levels were measured by means of a specific radioimmunoassay and were evaluated for Cmax, tmax, and AUC up to 4 and 24 h. Independent of the test day and the treatment cycle studied, mean maximum gestodene serum levels were found about 0.8 to 0.9 h after pill intake. During the first treatment cycle, mean values of Cmax, AUC(0-4h), and AUC(0-24h) amounted to 4.3 ng.ml-1, 9.3 ng.ml-1.h, and 27.3 ng.ml-1.h on test day 1; these values increased by 250-400% and by 300-500%, respectively, when days 10 and 21 were compared to day 1. On day 1 of the third treatment cycle, these pharmacokinetic parameters were higher by almost a factor of two as compared to the corresponding data obtained on the beginning of the first cycle whereas the increase of these values between day 1 and the subsequent test days (200-300%) was slightly lower in cycle 3 as compared to cycle 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Dibbelt
L
L
Institute of Biochemical Endocrinology, Medical University, Lübeck, Fed. Rep. of Germany.
Knuppen
R
R
Kuhnz
W
W
Jütting
G
G
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D003276:Contraceptives, Oral / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D009652:Norpregnenes / Q000493:pharmacokinetics*; D011485:Protein Binding; D011863:Radioimmunoassay; D012044:Regression Analysis; D012709:Serum Albumin / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
D001798:Blood Proteins; D003276:Contraceptives, Oral; D009652:Norpregnenes; D012709:Serum Albumin; D012738:Sex Hormone-Binding Globulin; C033273:Gestodene