title: Influence of high doses of vitamin C on the bioavailability and the serum protein binding of levonorgestrel in women using a combination oral contraceptive.
abstract: The absence of an effect of high oral doses of vitamin C on the systemic availability of ethinylestradiol in women using a levonorgestrel-containing combination oral contraceptive (0.15 mg levonorgestrel and 0.03 mg ethinylestradiol) was demonstrated in a recent study. However, it is conceivable that the oral administration of gram quantities of vitamin C could also interfere with the sulfation of levonorgestrel (LNG) metabolites during phase II biotransformation, because sulfates represent a major part of the conjugated metabolites of LNG in the serum. This possible interaction was investigated in the aforementioned study, comparing Cmax and AUC(0-12h) values of LNG on the first and 15th day of two successive treatment cycles with and without co-medication of vitamin C. In addition, the serum protein binding of LNG and the concentration of the binding proteins SHBG and CBG were compared between both treatments. Corresponding parameters obtained during treatment with the oral contraceptive alone and during co-administration of vitamin C were evaluated statistically for possible differences. No effect of vitamin C was observed for any of the parameters investigated. Thus, the repeated oral administration of gram quantities of vitamin C does not impair the sulfation of hydroxylated metabolites of LNG. There was also no observable effect on the serum protein binding of LNG and the concentrations of SHBG and CBG in the serum. The results obtained in this study population (American women) for LNG are in good agreement with those obtained from a previous study in European women, who had taken a combination oral contraceptive containing the same doses of LNG and ethinylestradiol.
authors.affiliation: Research Laboratories, Schering Aktiengesellschaft, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kuhnz
authors.forename: T
authors.initials: T
authors.lastname: Louton
authors.forename: M
authors.initials: M
authors.lastname: Hümpel
authors.forename: D J
authors.initials: DJ
authors.lastname: Back
authors.forename: N M
authors.initials: NM
authors.lastname: Zamah
mesh_terms: D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism*; D003277:Contraceptives, Oral, Combined; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000097:blood* / Q000493:pharmacokinetics*; D011485:Protein Binding; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014156:Transcortin / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D003277:Contraceptives, Oral, Combined; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D016912:Levonorgestrel; D014156:Transcortin; D001205:Ascorbic Acid