7-ethoxycoumarin deethylation activity in perfused isolated rat brain

7-ethoxycoumarin (7-EC) deethylation activity was measured in the perfused rat brain in situ. Infusion of 7-EC into a brain through an internal carotid artery resulted in the formation of 7-hydroxycoumarin (7-HC) and its conjugates in the effluent perfusate collected from the superior vena cava. The rate of formation of products was 200 nmol/h/g when 130 microM 7-EC was infused. This value was much higher (more than 100 times) than that determined from the brain microsomal activity ( approximately 1 nmol/h/g), indicating that the activity determined with microsomes was an underestimate. This value was comparable to the activity in the perfused liver (30-50%), suggesting that drug metabolizing enzymes can play important roles within the brain. Pretreatment of rats with P-450 inducers such as phenobarbital and beta-naphthoflavone increased the deethylation activity in the perfused brain, as in the perfused liver. We conclude that the perfused brain is suitable for evaluating drug metabolizing activities under physiological conditions.