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Pharmacokinetic parameters of sulfated tibolone metabolites in postmenopausal women after single and multiple doses of tibolone.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2007 Apr; Vol. 81 (4), pp. 573-9. Date of Electronic Publication: 2007 Feb 14. - Publication Year :
- 2007
-
Abstract
- The objective of this study was to determine pharmacokinetic parameters of sulfated tibolone metabolites after single dose and their accumulation after multiple doses of tibolone. Blood samples from postmenopausal women in a single-dose (2.5 mg tibolone), open-label study (n=8) and multiple-dose (placebo, 0.3, 0.625, 1.25, or 2.5 mg/day tibolone for twenty-six cycles of 28 days), randomized, double-blind study (n=15) were analyzed for non-sulfated and sulfated tibolone metabolites by validated gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with tanolam mass spectrometry (LC-MS/MS), respectively. The predominant non-sulfated and sulfated metabolites after a single dose were 3alpha-hydroxy-tibolone and 3alpha,17beta-di-sulfated (di-S)-tibolone. At 3 h, >90% of metabolites were sulfated. Tibolone and Delta(4)-tibolone were detectable for about 6 h. After multiple treatment cycles with different doses, metabolite levels at 10 h were dose-related and levels of di-S metabolites were three- to fivefold higher than after a single dose. Tibolone metabolite levels did not differ between cycles. Inactive di-S tibolone metabolites predominated in blood. No accumulation occurred between cycles 7 and 26.
- Subjects :
- Biotransformation
Double-Blind Method
Edetic Acid metabolism
Female
Gas Chromatography-Mass Spectrometry
Humans
Hydroxylation
Middle Aged
Norpregnenes administration & dosage
Selective Estrogen Receptor Modulators administration & dosage
Sulfates metabolism
Norpregnenes pharmacokinetics
Postmenopause metabolism
Selective Estrogen Receptor Modulators pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0009-9236
- Volume :
- 81
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 17301737
- Full Text :
- https://doi.org/10.1038/sj.clpt.6100094