In vitro biotransformation of pyrazinamide by rat liver: identification of a new metabolite

In addition to pyrazinoic acid and 5-hydroxypyrazinoic acid, a new metabolite of the tuberculostatic agent pyrazinamide, 5-hydroxypyrazinamide has been identified after in vitro incubation of the drug with rat liver preparations. The structure of the new metabolite was elucidated by GLC analysis and, after isolation by TLC, by MS analysis. Formation of the metabolite is mediated by soluble Xanthine oxidase and is an alternative pathway for pyrazinamide detoxification by the liver cell.