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.