CAFFEINE INCREASES ITS OWN METABOLISM THROUGH CYTOCHROME P4501A INDUCTION IN RATS

Caffeine is one of the most widely used - and maybe abused - xenobioti c compounds in the world. If numerous pharmacological properties of ca ffeine have been reported, the effects of caffeine treatment on the he patic drug-metabolizing enzyme system have been scarcely studied. Pret reatment of, rats for 3 days with 150 mg/kg/day of caffeine dramatical ly increased P4501A and P4502B dependent catalytic activities determin ed in vitro. Furthermore,: N-demethylations and C-8 oxidation of caffe ine were increased by about 2 fold by caffeine,treatment. Immunoblot a nalysis demonstrated that the liver contents of P4501A2 and P4502B1/2B 2, known to be involved in these monooxygenase activities, increased a lso by about 2 fold. Cytochrome P4503A1 and 2E1 were not modified. Tak en together, there data suggest that caffeine increases its own metabo lism through P4501A induction.