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, 3alpha-hydroxyl-7-methyl- norethynodrel (3alpha-HMN) and 3beta-hydroxyl-7-methyl-norethynodrel (3beta-HMN) in plasma were determined by using a validated liquid chromatography-mass spectrometry (LC-MS) method.
Results: The apparent elimination half-life (T½) of 3alpha-HMN was 1.43plusminus0.52 h, and that of 3beta-HMN was 1.53plusminus0.60 h. Maximum plasma concentrations (Cmax) were found to be 8.75plusminus4.36 mug/L for 3alpha-HMN and 3.59plusminus1.81 mug/L for 3beta-HMN. Areas under the plasma concentration versus time curve (AUC0-t) were 26.30plusminus12.14 mugdoth-1dotL-1for 3alpha-HMN and 9.89plusminus4.93 mugdoth-1dot L-1 for 3beta-HMN.
Conclusion: Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism in humans.
Keywords:
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, 3alpha-hydroxyl-7-methyl- norethynodrel (3alpha-HMN) and 3beta-hydroxyl-7-methyl-norethynodrel (3beta-HMN) in plasma were determined by using a validated liquid chromatography-mass spectrometry (LC-MS) method.
Results: The apparent elimination half-life (T½) of 3alpha-HMN was 1.43plusminus0.52 h, and that of 3beta-HMN was 1.53plusminus0.60 h. Maximum plasma concentrations (Cmax) were found to be 8.75plusminus4.36 mug/L for 3alpha-HMN and 3.59plusminus1.81 mug/L for 3beta-HMN. Areas under the plasma concentration versus time curve (AUC0-t) were 26.30plusminus12.14 mugdoth-1dotL-1for 3alpha-HMN and 9.89plusminus4.93 mugdoth-1dot L-1 for 3beta-HMN.
Conclusion: Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism in humans.