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

Biochem Biophys Res Commun. 1988 Apr 15;152(1):411-6. doi: 10.1016/s0006-291x(88)80729-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotransformation
  • Codeine / metabolism*
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / metabolism*
  • Humans
  • Kinetics
  • Microsomes, Liver / enzymology*
  • Mixed Function Oxygenases / metabolism*
  • Morphine / metabolism
  • Substrate Specificity


  • Morphine
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6
  • Codeine