To compare the inhibitory effectS of quinidine and quinine on liver microsome bufuralol 1Aydroxylase (BH). aryr hydrocarbon hydroxyl- ase (AHH). and 7-ethoxycoumarin O-deethylase (ED) activities in man and rat. METHODS: A normal phase HPLC and the fluorescence spectrometry were used to assay the enzyme activities. RESULTS: Both quinidine and quinine produced a concentration-dependent inhibition to liver microsome BH, AHH, and ED in man and rat. Thelr median inhibitory concentrations (ICsO) oii liver microscme BH, AHH. and ED low and high atfinjfy phases were 0.2. 378. 2952P and >5000 moI.L-1 for quinine in man. 290, 613 1465. 1595. UmoI.L-1 for quinidine in rat; 29, 207, 808, and >5000 umoI.L-l for quinine in man. and 31, 54, 597, and 2508 UmoI.L-1 for quinine in rat, respectively. CONCLUSlON: Quinidine is a species- and stereo-selective potent inhibitor to human liver microscme BH.

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.