Caffeine Metabolism Upon Sequential Recycling Perfusion of Isolated Rat Liver and Kidney

초록

Caffeine undergoes extensive metabolism in human and at least 11 metabolites are detected in urine. Hepatic enzymes like CYP1A2, 2A5, 2E1, 3A4, 3A5, flavin-containing monooxygenase (FMO), N-acetyltansferase 2 and xanthine oxidase (XO) are known to catalyze the production of the 11 caffeine metabolites identified in urine. Although not identified in urine. Although not identified, kidney is also known to contain some of the enzymes which may catalyze the caffeine metabolism and contribute to the production of the 11 urinary caffeine metabolites. Therefore, we have utilized the isolated perfused liver and kidney, each organ separately and in sequential combination, for the metabolism of caffeine to identify the tissue origin of the enzymes which are responsible for the production of the 11 urinary metabolites. Upon recycling perfusion of caffeine through the liver for 1 hr, 1,7,-dimethylurate (17U), theophylline (TP), paraxanthine (PX), trimethylurate (TMU) and theobromine (TB) were produced. Under the same perfusion condition, kidney could produce only small quantities of PX and TB. With sequential perfusion of both organs, the rates of PS, TP and TMU formations were increased only by 15 to 37%, but the rates of TB and 17U formation were not increased. These results indicated that the FMO and XO activities in kidney amy be minimal and do not contribute much to the overall in vivo caffeine metabolism. Therefore, most of the in vivo caffeine metabolism may occur in liver.