IN VITRO STUDIES ON OMEPRAZOLE METABOLISM IN RAT LIVER MICROSOMES

The matabolism of omeprazole to its two major metabolites,hydroxyonicprazolc(OH- OPZ )and omeprazole sulfone(OPZ-SFN )was studied in rat liver microsomcs by a reversedphase HPLC assay.The formation of metabolites of OPZ depcnded on incubation time,siibstrateconcentration,rnicrosomal protein concentration,and was found to be optimal at pH4.The vmaxand Km of OPZ hydroxylation in the rat liver microsomal preparation were 2033 nmol/(min.mgprotein) and 46.8μmol·L^-1respectively.The maximum rate of formation of OPZ-SFN( VMAX )was 187.9 nmol/(min·mg protein),with a Km value of l20.7μmol·L^-1in rat liver microsome,Moreover,the effects of 7 drugs on OPZ metabolism were tested。The resuIts showed thatmephenytoin,benzodiazepines(DZ,NDZ,TMZ,FNZ,NZ)and papaverine caused inhibition ofOPZ metabolism,among them papaverine was the only fairly strong inhibitor.