Abstract
Flurbiprofen (FP)-amino acid (L-arginine (Arg), L-lysine (Lys) and L-phenylalanine (Phe))ethyl esters were synthesized and the release of FP enantiomers from these compounds in the presence of trypsin (Tp), α-chymotrypsiin (ChTp)and carboxypeptidase (CP) A, CPR and CPY were examined. The ester bonds of these compounds were hydrolyzed rapidly by Tp or ChTp, suggesting that they are good substrates for these enzymes. FP(R) was released by CPB and CPY faster than FP (S) from the FP-basic amino acids, while FP-Phe-OH was not hydrolyzed at all by CPA. These results indicate the stereoselective carboxypeptidase-mediated release of FP enantiomers from the FP-basic amino acids. FP(S)-Arg-OH was separated from FP(R)-Arg-OH by high-performance liquid chromatography, The FP(S) was released by CPB and CPY from FP(S)-Arg-OH. it is therefore thought that FP(S)-Arg-OEt is utilized as an active water-soluble prodrug for FP.
