Abstract
Aim:
To investigate the stereoselectivity in human metabolic 3-reduction of tibolone.
Methods:
Twenty healthy Chinese female volunteers were given a single oral dose of tibolone (2.5 mg), and serial blood samples were collected after treatment. The plasma concentrations of the two pharmacologically active 3-hydroxyl metabolites of tibolone, 3α-hydroxyl-7-methyl- norethynodrel (3α-HMN) and 3β-hydroxyl-7-methyl-norethynodrel (3β-HMN) in plasma were determined by using a validated liquid chromatography-mass spectrometry (LC-MS) method.
Results:
The apparent elimination half-life (T½) of 3α-HMN was 1.43±0.52 h, and that of 3β-HMN was 1.53±0.60 h. Maximum plasma concentrations (Cmax) were found to be 8.75±4.36 μg/L for 3α-HMN and 3.59±1.81 μg/L for 3β-HMN. Areas under the plasma concentration versus time curve (AUC0-t) were 26.30±12.14 μg·h−1·L−1for 3α-HMN and 9.89±4.93 μg·h−1· L−1 for 3β-HMN.
Conclusion:
Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism in humans.
Similar content being viewed by others
Article PDF
References
Paola A, Raffaele DM, Ettore, Z . Tibolone: a review. Maturitas 1998; 30: 295–305.
Valdivial I, Ortega D . Mammographic density in postmenopausal women treated with tibolone, eatriol or conventional hormone replacement therapy. Clin Drug Invest 2000; 20: 101–7.
Lundstrom E, Christow A, Kersemaekers W, Svane G, Azavedo E, Soderqvist G, et al. Effects of tibolone and a continuous combined HRT regimen on mammographic breast density. Am J Obstet Gynecol 2002; 186: 717–22.
Sandker GW, Vos RME, Delbressine LPC, Slooff MJ, Meijer DK, Groothuis GM . Metabolism of three pharmacologically active drugs in isolated human and rat hepatocytes: analysi s of interspecies variability and comparison with metabolism in vivo. Xenobiotica 1994, 24: 143–55.
Vos REM, Krebbers SFM, Verhoeven CHJ, Delbressine LPC . The in vivo human metabolism of tibolone. Drug Metab Dispos 2002; 30: 106–12.
Schoonen, WG, Deckers GH, de Gooyer, ME, de Ries R, Kloosterboer HJ . Hormonal property of norethisterone, 7α-methyl-norethisterone and their derivative. J Steroid Biochem Mol Biol 2000; 74: 213–22.
Palacios, S . Tibolone: what does tissue specific activity mean? Maturitas 2001; 37: 159–65.
Kloosterboer, HJ . Tibolone: a steroid with a tissue-specific mode of action. J Steroid Biochem & Mol Biol 2001; 76: 231–8.
Timmer CJ, Verheul AM, Doorstam DP . Pharmacokinetics of tibolone in early and late postmenopausal women. Br J Clin Pharmacol 2002; 54: 101–6.
Zuo, M, Gao, MJ, Liu, Z, Cai, L, Duan, GL . p-Toluenesulfonyl isocyanate as a novel derivatization reagent to enhance the electrospray ionization and its application in the determination of two stereo isomers of 3-hydroxyl-7-methyl-norethynodrel in plasma. J Chromatogr B 2005; 814: 331–7.
Verhoeven CHJ, Vos REM, Delbressine LPC . The in vivo metabolism of tibolone in animal species. Eur J Drug Metab Pharmacokinet 2002; 27: 1–10.
Verhoeven CHJ, Krebbers SFM, Wagenaars GN, Vos RME . In vitro and in vivo metabolism of desgestrel in several species. Drug Metab Dispos 1998; 26: 927–36.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zuo, M., Gao, Mj., Liu, Z. et al. Stereoselectivity in metabolic 3-reduction of tibolone in healthy Chinese female volunteers. Acta Pharmacol Sin 26, 1527–1530 (2005). https://doi.org/10.1111/j.1745-7254.2005.00228.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2005.00228.x