Stereoselectivity in metabolic 3-reduction of tibolone in healthy Chinese female volunteers.
OBJECTIVE
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 (T(1/2) of 3alpha-HMN was 1.43+/-0.52 h, and that of 3beta-HMN was 1.53+/-0.60 h. Maximum plasma concentrations (C(max)) were found to be 8.75+/-4.36 microg/L for 3alpha-HMN and 3.59+/-1.81 microg/L for 3beta-HMN. Areas under the plasma concentration versus time curve (AUC(0-t)) were 26.30+/-12.14 microg.h(-1).L(-1) for 3alpha-HMN and 9.89+/-4.93 microg.h(-1).L(-1) for 3beta-HMN.


CONCLUSIONS
Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism in humans.
Zuo
Ming
M
Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, Shanghai 200032, China.
Gao
Ming-Jie
MJ
Liu
Zhen
Z
Cai
Lei
L
Duan
Geng-Li
GL
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D020847:Estrogen Receptor Modulators / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D009641:Norethynodrel / Q000031:analogs & derivatives / Q000097:blood; D009652:Norpregnenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
C500507:3-hydroxy-7-methyl-norethynodrel; D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D009641:Norethynodrel; C027385:tibolone