SUBCHRONIC TOXICITY OF PENTOSTATIN IN WISTAR RATS

Pentostatin, an adenosine deaminase inhibitor, has been approved for t he treatment of refractory hairy cell leukemia. In a preclinical toxic ity study, Wistar rats were administered 0, 1, 10, 25, and 50 mg/kg (0 , 6, 60, 150, and 300 mg/m(2), respectively) pentostatin intravenously once a week for 26 wk (1.5-75-fold above the therapeutic dose in huma ns). 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, respe ctively. Thyroiditis was still present 4 wk following drug withdrawal. Thyroiditis was characterized by glandular enlargement, follicular ep ithelial hyperplasia and degeneration, colloid depletion, and intersti tial infiltrates of lymphocytes and plasma cells. Drug-related changes in other tissues included lymphoid depletion of T-cell regions of thy mus, spleen, and lymph nodes; bronchiolization of alveolar ducts with accumulation of mucus and foamy macrophages; testicular atrophy with s perm granulomas; dermoepidermal lymphocytic infiltrates with ulceratio n and alopecia; and hepatocytomegaly.