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The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

Publication at First Faculty of Medicine |
2003

Abstract

This work describes the biotransformation of F enantiomers and DHF stereoisomers in isolated male guinea pig hepatocytes. Guinea pigs were chosen with respect to similarities in F metabolism as in Man found earlier.

R-F, S-F, (2R;4S)-DHF, (2S;4R)-DHF, (2S;4S)-DHF and (2R;4R)-DHF, structurally very similar compounds, served as substrates in order to observe their interaction with enzymes. Stereospecificity of the respective enzymes was studied in vitro, using hepatocytes monolayer.

Chiral HPLC using R,R-ULMO column as chiral stationary phase was used for detection and quantitation of metabolites. Conclusions: Different activities and stereospecificities of the respective enzymes were observed for each substrate in primary culture of hepatocytes.

Cell integrity is crucial for formation of secondary metabolites M-17203, UM-1 and UM-2.