Caffeine increases its own metabolism through cytochrome P4501A induction in rats.

Caffeine is one of the most widely used - and maybe abused - xenobiotic compounds in the world. If numerous pharmacological properties of caffeine have been reported, the effects of caffeine treatment on the hepatic drug-metabolizing enzyme system have been scarcely studied. Pretreatment of rats for 3 days with 150 mg/kg/day of caffeine dramatically increased P4501A and P4502B dependent catalytic activities determined in vitro. Furthermore, N-demethylations and C-8 oxidation of caffeine were increased by about 2 fold by caffeine treatment. Immunoblot analysis demonstrated that the liver contents of P4501A2 and P4502B1/2B2, known to be involved in these monooxygenase activities, increased also by about 2 fold. Cytochrome P4503A1 and 2E1 were not modified. Taken together, there data suggest that caffeine increases its own metabolism through P4501A induction.