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The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

Authors
Publisher
BioMed Central
Publication Date
Source
PMC
Keywords
  • Research Article
Disciplines
  • Biology
  • Chemistry

Abstract

1471-2210-3-5.fm ral ss BioMed CentBMC Pharmacology Open AcceResearch article The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes Radim Kral1, Lenka Skalova1, Barbora Szotakova1, Jakub Velik2, Ladislava Schroterova1, Yogeeta N Babu1 and Vladimir Wsol*1 Address: 1Department of Biochemical Sciences, Faculty of Pharmacy, Research Center LN00B125, Charles University, Hradec Kralove, Czech Republic and 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic Email: Radim Kral - [email protected]; Lenka Skalova - [email protected]; Barbora Szotakova - [email protected]; Jakub Velik - [email protected]; Ladislava Schroterova - [email protected]; Yogeeta N Babu - [email protected]; Vladimir Wsol* - [email protected] * Corresponding author Anti-inflammatory AgentsIsolated HepatocytesChiralityInversionHPLCEnantiomers Abstract Background: Flobufen (F) is an original nonsteroidal anti-inflammatory drug with one center of chirality. 4-Dihydroflobufen (DHF), compound with two chiral centers, is the main metabolite of F in microsomes and cytosol in all standard laboratory animals. 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. Results: (2R;4S)-DHF and (2S;4S)-DHF were the principle stereoisomers detected after incubation with rac-F, R-F and S-F. The ratio of (2R;4S)-DHF/(2S;4S)-DHF ranged from 1.1 to 2.4 depending on the substrate us

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