Stereospecific assay and stereospecific disposition of racemic carprofen in rats.
A procedure was developed for the separation and selective quantitative determination of the (S)(+)- and (R)(-)-enantiomers of the racemic anti-inflammatory drug carprofen as their diastereomeric l-(-)-alpha-methylbenzylamides. These derivatives are obtained in equivalent yields by reacint purified 14C-carprofen from biological specimens with l-(-)-alpha-methylbenzylamine via the 1,1'-carbonyldiimidazole intermediate, followed by extraction and differential radiometric quantitation of the TLC-separated diastereomers. In the rat, the (R)(-)-carprofen enantiomer was eliminated from blood and secreted in the bile as the ester glucuronide at a rate approximately twice that of the (S)-(+)-enantiomer, resulting in the accumulation of the pharmacologically more active (S)(+)-enantiomer in the rat blood. Evidence for an additional process favoring the elimination of the (R)(-)-enantiomer in the rat was derived from pharmacokinetic data evaluation.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D002227:Carbazoles / Q000097:blood / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D013237:Stereoisomerism; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D002227:Carbazoles; D005965:Glucuronates; C007005:carprofen