Toxicity of morphazinamide compared with pyrazinamide.

In a toxicological study on rats two derivatives of pyrazine: morphazinamide (MZA) and pyrazinamide (PZA) were compared with the objective to verify the possibility of using MZA as a substitute for the hepatotoxic PZA. The daily recorded weight and food intake of the rats were statistically significantly changed in the experimental groups with MZA as well as those with PZA, as compared with the control group and the group fed parallelly, already after the sixth dose of MZA and PZA 2.5 g per kg body weight, and similarly changed were also the various biochemical blood and liver tissue tests. Yet, certain differences were observed between the action of MZA and PZA. Some explanation was obtained from PZA blood and tissue concentrations, determined in the course of 24 hours following the administration of the sixth dose of both drugs. A repeated administration of MZA led to a PZA cumulation in the blood and organs of the rats. The study demonstrated that both drugs are hepatotoxic and, in high doses, also nephrotoxic. Moreover, MZA decreases the concentration of plasmatic iron and causes spleen atrophy. It will not be, therefore, a suitable substitute for the hepatotoxic PZA.