Acta Pharmacologica Sinica 2005 December; 26 (12): 1527-1530; doi: 10.1111/j.1745-7254.2005.00228.x

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, 3a-hydroxyl-7-methyl- norethynodrel (3a-HMN) and 3b-hydroxyl-7-methyl- norethynodrel (3b-HMN) in plasma were determined by using a validated liquid chromatography-mass spectrometry (LC-MS) method.

Results: The apparent elimination half-life (T_½) of 3a-HMN was 1.43±0.52 h, and that of 3b-HMN was 1.53±0.60 h. Maximum plasma concentrations (C_max) were found to be 8.75±4.36 μg/L for 3a-HMN and 3.59±1.81 μg/L for 3b-HMN. Areas under the plasma concentration versus time curve (AUC_0-t) were 26.30±12.14 μg· h^-1· L^-1 for 3a-HMN and 9.89±4.93 μg·h^-1· L^-1 for 3b-HMN.

Conclusion: Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism in humans.

Keywords: tibolone; metabolite; pharmacokinetics; stereoselectivity