Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of cigarette smoking

Clin Pharmacol Ther. 1991 Jan;49(1):44-8. doi: 10.1038/clpt.1991.8.


It has been realized recently that the primary metabolism of caffeine in humans is catalyzed by P-450IA2 and that the rate of caffeine metabolism can be estimated from a metabolic ratio in a single urine sample. A population of 178 students including 19 smokers were subjected to this caffeine test to establish their P-450IA2 index. Both stated numbers of cigarettes smoked per day and urinary cotinine levels as a confirmatory measure correlated significantly with enzyme activity showing dose-effect relationships (r = 0.62 and 0.89, respectively). Nevertheless, more nonsmokers than smokers had the highest enzyme indexes, suggesting that dietary elements or other factors may determine P-450IA2 activities in populations. Because P-450IA2 is a monooxygenase that may be confined to the liver, caffeine reveals directly the Ah-receptor-dependent enzyme induction only in the liver, but it may also be a signal of induction elsewhere.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Caffeine*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Enzyme Induction
  • Humans
  • Liver / enzymology
  • Oxidoreductases / biosynthesis*
  • Plants, Toxic*
  • Smoking / metabolism*
  • Tobacco*
  • Uric Acid / analysis
  • Xanthines / analysis


  • Xanthines
  • Uric Acid
  • Caffeine
  • 1-methylxanthine
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Cytochrome P-450 CYP1A2