Determination of Pyrazinamide. IV

Decomposition of Pyrazinamide in Intestinal Tract and the Change of Pyrazinamide in the Liver; chiefly by Perfusion through Surviving Rabbit Liver

Abstract

Decomposition of pyrazinamide in the digestive tract and the liver was examined and it was found that although this compound is stable in artificial gastric and enteric solutions, a part of it was decomposed to pyrazinoic acid by the enzyme solution of rabbit enteric membrane, acetone-dried powder of bovine enteric membrane, and homogenate of a rabbit liver. Perfusion experiments were conducted with excised liver of a rabbit and the concentration of pyrazinamide and pyrazinoic acid in the perfusion solution was determined at definite intervals by colorimetry. It was thereby found that a fair amount of pyrazinamide (ca. 100γ/cc.) was decomposed 5 minutes after the start of perfusion and that it changed almost completely into pyrazinoic acid by two hours of perfusion.