Stereoselective glucuronidation of (R)- and (S)-naproxen by recombinant rat phenol UDP-glucuronosyltransferase (UGT1A1) and its human orthologue

Abstract

Recombinant rat phenol UDP-glucuronosyltransferase (UGT1A1) conjugates (R)-naproxen at a much higher rate (> 17-fold) than its (S)-enantiomer, substantiating previous findings on stereoselective glucuronidation of racemic naproxen. In contrast, the recombinant human orthologue conjugated both enantiomers at equal rates. In line with high constitutive expression of UGT1A1 in extrahepatic tissues, a high R/S ratio of naproxen glucuronidation was found in rat testes, intestine, lung and kidney. The results demonstrate that (R)-naproxen represents a stereoselective substrate of rat UGT1A1, but not of the human orthologous UGT1A1.