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Abstract

The influence of clofibrate on the stereoconversion of fenoprofen (FPF) was studied in guinea pigs. This hypolipidaemic agent has been related to some biochemical changes in the liver leading to an increase in the chiral inversion process. Two groups of animals (n = 6 per group) were pretreated with oral doses of clofibrate (280 mg/kg per day) for three days and were then given (R)- or (S)-FPF (5 mg/kg, IV). The FPF enantiomers were extracted from the guinea-pigs' plasma using a solid phase procedure and analysed by HPLC with previous derivatization with L-leucinamide. Pretreatment with clofibrate increased the chiral inversion of (R)-FPF in favour of the pharmacologically active (S)-FPF enantiomer. Before this metabolic interaction can be applied to therapy with fenoprofen, the toxic effects of (S)-(+)-FPF on the gastrointestinal and renal tracts and the interference by (R)-(-)-FPF with the metabolism of lipids should be thoroughly evaluated.

Enantioselective determination of ibuprofen in plasma by high-performance liquid chromatography–electrospray mass spectrometry

“…Ibuprofen is extensively metabolized via the oxidation and glucuronidation routes showing selectivity for (+)-(S)-ibuprofen. In addition, unidirectional inversion of the (−)-(R)-to (+)-(S)-enantiomer also occurs in vivo [2,[4][5][6]. As a consequence, plasma concentrations of (−)-(R)-and (+)-(S)-ibuprofen differ significantly, resulting in stereoselective pharmacokinetic parameters [5].…”

Biosynthesis and stereoselective analysis of (−)- and (+)-zaltoprofen glucuronide in rat hepatic microsomes and its application to the kinetic analysis

“…Previously studies indicated that the effect on cyclo-oxygenase of fenoprofen and ketoprofen were resulted from the S-(+) enantiomer [28,29]. Among them, the metabolic chiral inversion process corresponds to a selective unidirectional transformation from the inactive R-(−) to the active S-(+) enantiomer [30,31]. Therefore, we may presume that with the incubation time expanding, the possible metabolic chiral transformation inverses and exacerbates the stereoselective glucuronidation of ZPF in rat liver microsomes.…”

Homochiral Drug Design and Development by Racemization

“…In various animal species and human beings, ibuprofen has been studied widely with unidirectional chiral inversion [35, 67-69, 75, 76-83]. The unidirectional chiral inversion of R-fenoprofen to its active antipode, with high interspecies variation in the inversion magnitude, was reported in rat [16,[84][85][86], guinea pig [86,87], cat [88], and humans [89,90]. In rats [91] and humans [92], benoxaprofen showed stereospecific inversion from R-to S-enantiomer with a higher inversion rate in rats than in humans.…”