Studies on the metabolism of ibuprofen in isolated rat hepatocytes.

Ibuprofen (IBP) was used to demonstrate that freshly isolated rat hepatocytes offer a suitable model to investigate the oxidative metabolism of antiinflammatory 2-arylpropionic acids (profens). The formation of two major oxidative metabolites of IBP (metabolite A--hydroxyibuprofen and metabolite B--carboxyibuprofen) was observed with the use of rat hepatocytes. The incubation of ibuprofen with a suspension of rat hepatocytes in Hanks' buffer during 60 min. resulted in a decrease of racemic IBP and both R(-)-IBP and S(+)-IBP concentration coincided with the appearance of its major racemic metabolites (metabolite A and metabolite B). The relative abundance of the above IBP metabolites produced by hepatocytes was consistent with their quantitative profiles in vivo in rat. The results confirm the value of isolated hepatocytes as a predictive model for the in vivo metabolism pattern of profens.