Technical Report on the Subchronic Toxicity Study of 3'-Azido-3'-dioxythymidine (AZT) and Pyrazinamide Combinations Administered by Gavage to B6C3F1 Mice (NIEHS AIDS Therapeutics Toxicity Report 5)

Abstract

The toxicity of combinations of AZT (200 or 400 mg) and pyrazinamide (1,000 or 1,500 mg) was evaluated in B6C3F1 mice treated by gavage for up to 94 days. The primary toxic effect of AZT was bone marrow suppression manifested by macrocytic anemia, thrombocytosis, and reticulocytopenia followed by reticulocytosis. Cellular depletion of bone marrow was observed microscopically. Administration of pyrazinamide alone caused mild hepatotoxicity, as evidenced by increased liver weights and by glycogen depletion of hepatocytes in a zonal pattern. AZT and pyrazinamide administered together resulted in a significant exacerbation of the hematopoietic toxicity induced by AZT alone. The hepatotoxicity of pyrazinamide was slightly augmented by AZT.