[2-14C]caffeine metabolism in control and 3-methylcholanthrene induced rat liver microsomes by high pressure liquid chromatography

Theobromine, theophylline, paraxanthine and 1,3,7-trimethyluric acid were identified as caffeine metabolites after incubation of [2-¹⁴C]caffeine with rat liver microsomes and separation by high-pressure liquid chromatography (HPLC). A 9-fold induction of caffeine metabolism was observed in 3-methylcholanthrene (MC)-induced microsomes and this induction ranged from 4 to 11 times for individual metabolites. Induction of aryl hydrocarbon hydroxylase (AHH) was about 5-fold, comparable to that of theophylline formation. Primary caffeine metabolism is an enzymic process catalyzed by the microsomal mixed-function oxidases.