Aim: To study the ability of oxidizing metoprolol (Met) to form alpha-hydroxymetoprolol (HM) in Chinese in vivo and in vitro.
Methods: An ion-pair reverse phase high performance liquid chromatography was used.
Results: In vivo study, the 8-h urinary recoveries of Met and HM after po Met tartrate 100 mg were tested in 96 unrelated healthy Chinese Han volunteers, and the capacity of Met alpha-hydroxylation expressed by lg Met/HM (metabolic ratio, MR). The frequency histogram of lg MR showed the characteristic bimodal distribution of monogenic control variation, and the phenotypical antimode of lg MR was 1.09. Only 1 man with lg MR = 2.30 was identified as poor metabolizer of Met alpha-hydroxylation. The urinary recoveries of Met and HM and the MR in 95 extensive metabolizer were 6.8 +/- 3.3%, 3.0 +/- 1.5% of dose mole and 3.1 +/- 2.5, respectively. The sex difference, 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 alpha-hydroxylase. The enzyme kinetics parameters were Km = 89.60 mumol L-1 and Vmax = 39.5 ng HM mg-1 min-1. No functional absence of liver microsome Met alpha-hydroxylase was found in the tested liver samples from 8 people, and the activities of liver microsome Met alpha-hydroxylase were 31 +/- 22 ng mg-1 min-1.
Conclusion: The incidence of poor metabolizer phenotype for Met alpha-hydroxylation in Chinese Han nationality is low, and the NADH is not involved in human liver microsome Met alpha-hydroxylation.