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‐(‐)‐α‐methylbenzylamides. These derivatives are obtained in equivalent yields by reacting purified 14C‐carprofen from biological specimens with l‐(‐)‐α‐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. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company