Stereoselectivity in metabolic 3-reduction of tibolone in healthy Chinese female volunteers

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 (T 1/2) 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-1 for 3α-HMN and 9.89±4.93 μg·h-1·L-1 for 3β-HMN. Conclusion: Stereoselective differences exist in the pharmacokinetics of tibolone metabolism in humans. ©2005 CPS and SIMM.