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- W1990801024 abstract "Flurbiprofen is a chiral 2-arylpropionate used clinically as a racemate. Previously a significant pharmacokinetic interaction between the enantiomers of flurbiprofen has been reported in both rats and humans. The possible mechanism for this interaction was believed to involve competitive protein binding between the enantiomers. In addition, the saturable binding of flurbiprofen enantiomers in vitro in human plasma has been demonstrated. In this study different doses of racemic flurbiprofen were administered to rats to create differing extents of competition for protein binding sites between the enantiomers. There was a statistically significant dose-dependent increase in total body clearance and volume of distribution of both the Rand Senantiomers. However, there was no change in either the S/R AUC ratio or the elimination rate constants for (R) or (S)-flurbiprofen with increasing dose. These results are consistent with the hypothesis that the increasing amount of (R) and (S)-flurbiprofen in the body causes displacement of flurbiprofen enantiomers from their protein binding sites, resulting in their increased total body clearance and volume of distribution. Further, the data suggest that previously reported extents of Rto Senantiomeric inversion for other 2-arylpropionates may not be accurate if the enantiomers exhibit nonlinear kinetics or there is a significant kinetic interaction between the enantiomers." @default.
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- W1990801024 date "1994-08-01" @default.
- W1990801024 modified "2023-10-07" @default.
- W1990801024 title "Dose-Dependency of Flurbiprofen Enantiomer Pharmacokinetics in the Rat" @default.
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- W1990801024 doi "https://doi.org/10.1002/jps.2600830804" @default.
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