Metabolism Of Four Drugs In Cunninghamella Models

According to the metabolism of four drugs: osalmide, etofesalamide, pantoprazole and lornoxicam in mammalian and by seeing about Cunninghamella elegans, C.blakesleana and C.echinulata's abilities to transform them, their microbial transformation models for drug metabolism were set up and the similarities and differences between microbe and mammalian were compared. By means of the probe substrate and the specific inhibitor of human cytochrome P450 2C9, the drug metabolic enzyme for lornoxicam in C. elegans AS3.2028 was compared with CYP2C9. 1. Metabolism of osalmide and etofesalamide in microbial models Microbial models were used to study phase II metabolism of osalmide and etofesalamide. Filamentous fungi, which were mainly Cunninghamella , were selected as transformation strains and the metabolites of osalmide and etofesalamide were assayed by liquid chromatography-tandem mass spectrometry (LC/MS~n). Osalmide and etofesalamide were both transformed into two phase II metabolites, glucoside conjugate and pentoside conjugate. Glucoside conjugate was the major product and no phase I metabolites were produced. Enzymatic hydrolysis experiment was made to testify further the structure of etofesalamide glucoside conjugate. The study showed that Cunninghamella may serve as useful models in vitro for the study of phase II metabolism of osalmide and etofesalamide; etofesalamide glucoside conjugate produced in microbial models, which was different from etofesalamide glucuronide conjugate produced in rabbits, indicated the trait of phase II metabolism in microbe.