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Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI)

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Published in Biochemical and Biophysical Research Communications. 1988, vol. 152, no. 1, p. 411-6
Abstract 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 of the reaction in one extensive metabolizer's microsomes was 149 microM and Vmax 17.6 nmol X mg P-1 X hour-1 versus greater than 1 mM and 1.6 nmol X mg P-1 X hour-1 respectively in one poor metabolizer. In vitro morphine production was competitively inhibited by quinidine (Ki 15 nM), the selective inhibitor of cytochrome P-450 dbl/bufI. There was also an excellent correlation between dextromethorphan O-demethylation, a prototype reaction for cytochrome P-450 dbl/bufI activity, and codeine O-demethylation. These data allow to conclude that codeine bioactivation to morphine is dependent on the polymorphic monooxygenase known as cytochrome db1/bufI.
Keywords BiotransformationCodeine/metabolismCytochrome P-450 CYP2D6Cytochrome P-450 Enzyme System/metabolismHumansKineticsMicrosomes, Liver/enzymologyMixed Function Oxygenases/metabolismMorphine/metabolismSubstrate Specificity
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PMID: 3358767
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Research group Groupe Desmeules Jules (pharmacologie/toxicologie) (567)
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DAYER, Pierre et al. Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI). In: Biochemical and Biophysical Research Communications, 1988, vol. 152, n° 1, p. 411-6. https://archive-ouverte.unige.ch/unige:92728

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