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Stereospecific inversion of (R)-(-)-benoxaprofen in rat and man
European Journal of Drug Metabolism and Pharmacokinetics
|January 1, 1980
Summary
Rats and humans convert (R)-(-)-benoxaprofen to its S-(+)-enantiomer. This stereospecific inversion occurs much faster in rats than in humans, with gut wall involvement suggested in rats.
Area of Science:
- Pharmacology
- Drug Metabolism
- Stereochemistry
Background:
- Benoxaprofen exists as enantiomers with differing pharmacological activities.
- Stereospecific inversion is a known metabolic pathway for some chiral drugs.
Purpose of the Study:
- To investigate the stereospecific inversion of (R)-(-)-benoxaprofen in rats and humans.
- To determine the rate and potential site of this metabolic transformation.
Main Methods:
- In vivo studies in rats and humans to observe enantiomer conversion.
- In vitro studies using everted intestinal sac preparations from rats.
Main Results:
- Both rats and humans stereospecifically invert (R)-(-)-benoxaprofen to (S)-(+)-benoxaprofen.
- The inversion rate is significantly faster in rats (t½ ≈ 2.5 h) compared to humans (t½ ≈ 108 h).
- Inversion in rats does not appear to occur in the liver but is facilitated by the intestinal wall in vitro.
Conclusions:
- The gut wall is a likely site for the rapid stereospecific inversion of benoxaprofen in rats.
- Species-specific differences in drug metabolism rates are significant, impacting pharmacokinetic profiles.