BIOTRANSFORMATION OF ETHEOFAZINE IN HEPATIC SUBCELLULAR FRACTIONS FROM RAT, DOG AND MONKEY

AIM: To study the biotransformation and its species differences of etheofazine, a new anticancer drug, in hepatic subcellular fractions. METHODS: The concentration of etheofazine and its metabolite in hepatic 9 000×g supernatant fractions (S-9) and microsomes were determined with HPLC method. RESULTS: Enzyme kinetics studies of etheofazine in rat, dog and monkey liver S-9 indicated that the in vitro liver intrinsic clearance was 14.9, 10.4 and 30.4 μL·min^-1 ·mg^-1 protein, respectively. The metabolite formed in hepatic microsome was shown to be 7 ethyl 8 aminotheophylline(EAT). CONCLUSION: The insignificant species differences in metabolic profile of etheofazine can be anticipated. The results suggest that hepatic subcellular fractions are useful as in vitro models for species difference study.