Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man

1. In the present study, nine cytochrome P450 enzyme activities in seven sp ecies were characterized to allow a practical means of comparing this impor tant metabolic step between various test animals and man. 2. Enzyme activities and kinetic parameters were first determined towards m arker substrates for human cytochrome P450 enzymes. Inhibition profiles wer e then determined with both antibodies directed against various cytochrome P450 enzymes and with chemical inhibitors. 3. Both the enzyme kinetic parameters/enzyme activities, and the inhibition profiles obtained for the animal species were compared with those obtained for human liver microsomes in order to postulate the animal species most s imilar to man with regard to each individual cytochrome P450 enzyme activit y. 4. It was found that, as expected, none of the tested species was similar t o man for all the measured P450 enzyme activities, but that in each species only some of the P450 enzyme activities could be considered as similar to man. 5. When it is known which human cytochrome P450 enzymes are involved in the metabolism of a compound, the comparative data presented here can be used for selecting the most suitable species for in vitro and in vivo experiment s.