Inhibitory effects of quinidine and quinine on liver microsome oxidation enzymes in man and rat.
OBJECTIVE
To compare the inhibitory effects of quinidine and quinine on liver microsome bufuralol 1'-hydroxylase (BH), aryl hydrocarbon hydroxylase (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. Their median inhibitory concentrations (IC50) on liver microsome BH, AHH, and ED low and high affinity phases were 0.2, 378, 2952, and > 5000 mumol.L-1 for quinine in man, 290, 613, 1465, 1595, mumol.L-1 for quinidine in rat; 29, 207, 808, and > 5000 mumol.L-1 for quinine in man, and 31, 54, 597, and 2508 mumol.L-1 for quinine in rat, respectively.


CONCLUSIONS
Quinidine is a species- and stereo-selective potent inhibitor to human liver microsome BH.
Tu
Z G
ZG
Department of Clinical Biochemistry, Chongquing University of Medical Sciences, China.
Zhao
L L
LL
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity
D003577:Cytochrome P-450 Enzyme System; D011803:Quinine; D006899:Mixed Function Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; C043872:bufuralol 1'-hydroxylase; D011802:Quinidine