title: Pharmacokinetics of the contraceptive steroids levonorgestrel and gestodene after single and multiple oral administration to women.
abstract: Little is known about the pharmacokinetics of the two progestins levonorgestrel and gestodene during long-term administration compared with single-dose pharmacokinetics. The predictive value of single-dose administration for the pharmacokinetic behavior of a progestin during long-term treatment was investigated for two triphasic oral contraceptives. One contained levonorgestrel and the other gestodene, each in combination with ethinyl estradiol. In eight Japanese women who received the levonorgestrel-containing formulation over a treatment cycle, steady-state trough levels of levonorgestrel were higher than those obtained by computer simulation based on single-dose administration. An analogous observation was made in a group of 10 white women who received the gestodene-containing formulation. A close correlation between gestodene and sex hormone-binding globulin concentrations was demonstrated for eight subjects; the other two patients already had initially high sex hormone-binding globulin levels. Ethinyl estradiol-induced production of sex hormone-binding globulin seems to be a major factor that contributes to the accumulation of the two progestins in the plasma. Computer simulation, based on single-dose pharmacokinetics, allows an estimation of this contribution.
authors: Research Laboratories, Schering AG, Berlin, West Germany.
authors: W
authors: W
authors: Kuhnz
mesh_terms: D000328:Adult; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007564:Japan; D016912:Levonorgestrel; D008657:Metabolic Clearance Rate; D009644:Norgestrel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009652:Norpregnenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
chemical_list: D003276:Contraceptives, Oral; D009652:Norpregnenes; D012738:Sex Hormone-Binding Globulin; C033273:Gestodene; D009644:Norgestrel; D016912:Levonorgestrel