Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2

Pharmacogenetics. 1996 Aug;6(4):291-6. doi: 10.1097/00008571-199608000-00002.


We investigated the involvement of CYP1A2 in the pharmacokinetics and metabolism of caffeine using mice lacking its expression (CYP1A2 -/-). The half-life of caffeine elimination from blood was seven times longer in the CYP1A2 -/- than wild-type mice. The clearance was concomitantly eight times slower. No parameter that could affect the pharmacokinetics differed between CYP1A2-/-and wild-type mice such as creatinine for kidney function; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin for liver function; or albumin for protein binding. Other P450s CYP2A, 2B, 2C, 2EI, and 3A were also unchanged in the knockout animals. Caffeine 3-demethylated metabolites thought previously to be characteristic of CYP1A2 (especially 1-methylxanthine and I-methylurate) were also found in the urines of the CYP1A2-/-animals, although at 40% of the level found in wild-type mice. These data indicate that the clearance of caffeine in wild-type mice is primarily determined by CYP1A2.

MeSH terms

  • Animals
  • Area Under Curve
  • Caffeine / blood
  • Caffeine / pharmacokinetics*
  • Caffeine / urine
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP1A2 / genetics
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Male
  • Mice
  • Mice, Knockout


  • Caffeine
  • Cytochrome P-450 CYP1A2