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期刊论文
M etoprolol α-hydroxylation capacity in 96 Chinese Han volunteers
中国药理学报,1995,16(4):325-329,-0001,():
AIM: To study the ability of oxidizing meto-proloi (Met) to form α-hydroxymetoprolol (HM) in Chinese in vivo and in vitro. METHODS: An ion pair reverse phase high performance liquid chromatography was used. RESULTS: In v/vo study, the 8-h urinary recoveries of Met and HM after po Met tartrate 100 mg were tested in 96 unrelated healthy Chinese Hart volunteers, and the capaeity of Met α-hydroxylation expressed by lg Met/HM (metabolic ratio. MR). The frequency histogram of lg MR showed the characteristic hi modal distribution of monogenie control variation, and the phenotypieal antinaode of lg MR was 1.09. Only 1 man with lg MR=2,30 was identified as poor metabolizer of Met α-hydroxylation, The urinary recoveries of Met and HM and the MR in 95 extensive metabohzer were 6.8±3.3%. 3.0±1.5% of dose mole and 3.1±2. 5; respectively, The sex difierence, smoking and tea consuming had no effects on the urinary excretions of Met, and HM. and the MR, In vitro, the adding of NADH did not affect the activities of human liver microsome Met α-hydroxylase. The enzyme kinetics parameters were Km=89.60 umol L-1 and Vmax=39.5 ng HM mg-1 min-1. No functional absence of liver mierosome Met α-hydroxylase was found in the tested liver samples from 8 people, and the activities of liver mierosome Met α-hydroxylase were 31 ±22ng mg-1 min-1, CONCLUSION: The incidence of poor metabolizer phenotype for Met α-hydroxylation in Chinese Hart nationality is low, and the NADH is riot involved in human liver microsome Met α-hydroxylation.
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