DIFFERENCE BETWEEN IN-VIVO AND IN-VITRO EFFECTS OF PROPOFOL ON DEFLUORINATION AND METABOLIC-ACTIVITIES OF HAMSTER HEPATIC CYTOCHROME P450-DEPENDENT MONO-OXYGENASES

We have compared the in vivo and in vitro effects of propofol on cytoc hrome P450-dependent monooxygenase activities in hamster liver microso mes. Propofol (Diprivan) 10 mg/100 g body weight was injected i.p, twi ce a day for 2 weeks to induce cytochrome P450 enzymes. Liver microsom es were prepared by differential centrifugation. Metabolism of the cyt ochrome P450-dependent mono-oxygenase system was evaluated by measurin g aniline hydroxylation, benzphetamine demethylation and benzo(a)pyren e hydroxylation. Defluorination of enflurane was assayed by detecting free fluoride metabolites. At similar concentrations as in the in vivo group, propofol in vitro exhibited concentration-dependent inhibition of metabolism of benzphetamine and benzo(a)pyrene. Aniline hydroxylat ion and defluorination of enflurane were inhibited to 78% of control w ith propofol 0.25 mmol litre(-1). In propofol-treated hamsters, was mi nimal inhibitory or inductive only either mono-oxygenase activities or capacity for defluorination. This difference between the in vitro and in vivo effects of propofol on cytochrome P450 mono-oxygenase activit ies emphasizes the need for care when comparing in vitro and clinical data.