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

• 作 者: Ming ZUO Ming-jie GAO Zhen LIU Lei CAI Geng-li DUAN
• 机 构: Laboratory for Chemical Defense and Microscale Analysis, Zhijiang 443200, China“,”Department of Phar
• 出 处: 中国药理学报(英文版)
• 发表日期: 2005年12期
• 关键词: tibolone metabolite pharmacokinetics stereoselectivity

Aim: To investigate the stereoselectivity in human metabolic 3-reduction oftibolone. Methods: Twenty healthy Chinese female volunteers were given a singleoral dose of tibolone (2.5 mg), and serial blood samples were collected aftertreatment. 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 determinedby using a validated liquid chromatography-mass spectrometry (LC-MS) method.Results: The apparent elimination half-life (T1/2) of 3α-HMN was 1.43±0.52 h, andthat of 3β-HMN was 1.53±0.60 h. Maximum plasma concentrations (Cmax) werefound to be 8.75±4.36 μg/L for 3α-HMN and 3.59±1.81 μg/L for 3β-HMN. Areash-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.