Subchronic toxicity of pentostatin in Wistar rats.

Abstract

Pentostatin, an adenosine deaminase inhibitor, has been approved for the treatment of refractory hairy cell leukemia. In a preclinical toxicity study, Wistar rats were administered 0, 1, 10, 25, and 50 mg/kg (0, 6, 60, 150, and 300 mg/m2, respectively) pentostatin intravenously once a week for 26 wk (1.5-75-fold above the therapeutic dose in humans). Lymphoplasmacytic thyroiditis was present in 20% of females given 25 mg/kg and in 20 and 47% of males and females given 50 mg/kg, respectively. Thyroiditis was still present 4 wk following drug withdrawal. Thyroiditis was characterized by glandular enlargement, follicular epithelial hyperplasia and degeneration, colloid depletion, and interstitial infiltrates of lymphocytes and plasma cells. Drug-related changes in other tissues included lymphoid depletion of T-cell regions of thymus, spleen, and lymph nodes; bronchiolization of alveolar ducts with accumulation of mucus and foamy macrophages; testicular atrophy with sperm granulomas; dermoepidermal lymphocytic infiltrates with ulceration and alopecia; and hepatocytomegaly.

• Authors: C L Courtney, K L Hawkins, C E Rothwell
• Journal: Toxicologic pathology (Toxicol Pathol) 1994 Sep-Oct Vol. 22 Issue 5 Pg. 519-23 ISSN: 0192-6233 [Print] United States
• PMID: 7899780 (Publication Type: Journal Article)

Chemical References

• Pentostatin

Topics

• Animals
• Female
• Lung (drug effects)
• Lymphoid Tissue (drug effects)
• Male
• Organ Size (drug effects)
• Pentostatin (administration & dosage, toxicity)
• Rats
• Rats, Wistar
• Thyroid Gland (drug effects)