In:
Chirality, Wiley, Vol. 13, No. 10 ( 2001-01), p. 754-759
Abstract:
Flobufen (F) is the original nonsteroidal antiinflammatory drug (NSAID) containing two enantiomers. The aim of this investigation was to elucidate the biotransformation pathway of F at chiral level in phase I of biotransformation. Stereoselectivity and stereospecificity of the respective enzymes were studied in male rats in vitro (microsomal and cytosolic fractions, hepatocytes suspension) and in vivo. The rac ‐F, (+)‐R‐F and (−)‐S‐F were used as substrates. Amounts of F enantiomers, 4‐dihydroflobufen diastereoisomers (DHF) and other metabolites (M‐17203, UM) were determined with a chiral HPLC method in two chromatographic runs on R,R‐ULMO and allyl‐terguride bonded columns. Stereoselective biotransformation of the two enantiomers of F was observed at all tested levels and significant bidirectional chiral inversion of enantiomers of F was observed in hepatocytes. Mean enantiomeric ratios of F concentrations (S‐/R‐), after rac ‐F incubations, ranging from 1.09 in cytosolic fraction to 18.23 in hepatocytes. Stereospecificity of the respective F reductases was also observed. (2R;4S)‐DHF and (2S;4S)‐DHF are the principal metabolites of F in microsomes and hepatocytes. Neither DHF diastereoisomers nor M‐17203 were found in cytosolic fraction. Only the nonchiral metabolite, M‐17203, was found in all urine and feces samples after oral administration of F. Chirality 13:754–759, 2001. © 2001 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0899-0042
,
1520-636X
Language:
English
Publisher:
Wiley
Publication Date:
2001
detail.hit.zdb_id:
2001237-8
SSG:
12
SSG:
15,3
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