Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI)
作者： Pierre Dayer , Jules Desmeules , Thierry Leemann , Rita Striberni
DOI: 10.1016/S0006-291X(88)80729-0
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摘要: Codeine O-demethylation to its active moiety morphine was investigated in human liver microsomes from 1 poor and 5 extensive metabolizer subjects (debrisoquine-type of oxidation polymorphism). Apparent Km the reaction one metabolizer's 149 microM Vmax 17.6 nmol X mg P-1 hour-1 versus greater than mM 1.6 respectively metabolizer. In vitro production competitively inhibited by quinidine (Ki 15 nM), selective inhibitor cytochrome P-450 dbl/bufI. There also an excellent correlation between dextromethorphan O-demethylation, a prototype for dbl/bufI activity, codeine O-demethylation. These data allow conclude that bioactivation is dependent on polymorphic monooxygenase known as db1/bufI.
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