[Synergistic effect of rifampicin on hepatotoxicity of isoniazid].

It was shown in experiments on male albino rats that rifampicin potentiated the hepatotoxicity of isoniazid. As compared to the use of isoniazid alone, its combination with rifampicin resulted in a higher activity of transaminases and alkaline phosphatases and a higher rate of inhibition of biliary secretion and synthesis and excretion of bile acids, bilirubin and cholesterol with bile. Moreover, an increase was observed in the level of lipid peroxidation products of the hepatocyte membranes in liver homogenates and blood, which was indicative of an increased intensity of lipid peroxidation. The increased hepatotoxicity of isoniazid was evident from a more pronounced decrease in the number of sulfhydryl groups accompanied by an increase in the number of disulfide ones in the liver and blood. The authors suggest that potentiation of isoniazid hepatotoxicity under the action of rifampicin was due to its inducing activity with respect to the microsomal oxidation enzymes.