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Species differences in the chirality of the carbonyl reduction of [ 14 C] fenofibrate in laboratory animals and humans
Author(s) -
Weil Andre,
Caldwell John,
Guichard JeanPierre,
Picot Gerard
Publication year - 1989
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530010304
Subject(s) - chemistry , fenofibrate , enantiomer , diastereomer , enantioselective synthesis , chirality (physics) , stereoselectivity , urine , chromatography , stereochemistry , organic chemistry , biochemistry , pharmacology , medicine , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark , catalysis
The prochiral carbonyl group of fenofibrate (isopropyl 2‐[4‐(4‐chlorobenzoyl)phenoxy]‐2‐methyl propionate) is reduced during its metabolism giving rise to a chiral secondary alcohol, “reduced fenofibric acid.” Chiral and diastereomeric HPLC methods have been developed for the determination of its enantiomeric composition and these have been applied to the measurement of the “reduced fenofibric acid” enantiomers in urine of rats, guinea pigs, dogs, and human volunteers given [ 14 C]fenofibrate. In the three animal species, the reduction is markedly enantioselective for the (–)‐isomer, the enantiomeric ratios (–/ +) being 95:5. This was not due to differences in the excretion of the enantiomers, since when racemic “reduced fenofibric acid” was given to rats it was recovered in the urine with the same enantiomeric composition as the dose form. In humans the ratio was 52:48 showing the lack of stereoselectivity of reduction in this species.