Open AccessStereoselectivity in metabolic 3‐reduction of tibolone in healthy Chinese female volunteers
Author(s) -
ZUO Ming,
GAO Mingjie,
LIU Zhen,
CAI Lei,
DUAN Gengli
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00228.x
Subject(s) - tibolone , pharmacokinetics , chemistry , plasma concentration , stereoselectivity , chromatography , medicine , organic chemistry , menopause , catalysis
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 (C max ) were found to be 8.75±4.36 μg/L for 3μ‐HMN and 3.59±1.81 μg/L for 3β‐HMN. Areas under the plasma concentration versus time curve (AUC o‐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: Stereo‐selective differences exist in the pharmacokinetics of tibolone metabolism in humans.