Subchronic toxicity of pentostatin in Wistar rats.
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.
Courtney
C L
CL
Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105.
Hawkins
K L
KL
Rothwell
C E
CE
D000818:Animals; D005260:Female; D008168:Lung / Q000187:drug effects; D008221:Lymphoid Tissue / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D015649:Pentostatin / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000187:drug effects*
D015649:Pentostatin