Abstract

AZT

Molecular Formula: C₁₀H₁₃N₅O₄

Molecular Weight: 267.24

CAS No.: 30516-87-1

Pyrazinamide

Molecular Formula: C₅H₅N₃O

Molecular Weight: 123.12

CAS No.: 98-96-4

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.

Contents

• Foreword
• Contributors
• Peer Review
• Introduction
  • Study Rationale
• Materials and Methods
  • Procurement and Characterization of Chemicals
  • Dose Formulations
  • Study Design
  • Statistical Methods
• Results
  • Survival and Clinical Findings
  • Body and Organ Weights
  • Hematology
  • Necropsy Observations
  • Histopathologic Observations
  • Sperm Motility and Vaginal Cytology Evaluations
• Discussion and Conclusions
  • Conclusions
• References
• Appendixes
  • APPENDIX A. Hematology Results
  • APPENDIX B. Organ Weights and Organ-Weight-to-Body-Weight Ratios
  • APPENDIX C. Reproductive Tissue Evaluations