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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(Tw)of 3α-HMN was 1.43±0.52 h,andthat of 3β-HMN was 1.53±0.60 h.Maximum plasma concentrations(C_(max))werefound to be 8.75±4.36 μg/L for 3α-HMN and 3.59+ 1.81 μg/L for 3β-HMN.Areasunder the plasma concentration versus time curve(AUC_(0-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 inhumans.
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 aftertreatment. Plasma concentrations of the two pharmacologically active 3 3-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 (Tw) 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 3α-HMN and 3.59 + 1.81 μg / L for 3β-HMN.Areasunder the plasma concentration versus time curve (AUC_ (0-t)) were 26.30 ± 12.14 μg.h -1 · L ~ (-1) for 3α-HMN and 9.89 ± 4.93 μg · h -1 (-1) for 3β-HMN.Conclusion: Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism inhumans.