Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methyl-CCNU, a compound with marked antitumor activity against the solid Lewis lung tumor in mice, was submitted to a preclinical pharmacologic evaluation. The toxicity of a single iv infusion was tested in 37 beagle dogs and 21 rhesus monkeys. The minimum lethal dose (LD) in dogs was 14 mg/kg and five of six dogs died within 7-10 days after treatment from hematopoietic toxicity with neutropenia, lymphopenia, anemia, and concomitant sepsis. Metaplasia of the intestinal epithelium also occurred. Thrombocytopenia was not observed. Dogs treated with 9.27-1.56 mg/kg exhibited reversible neutropenia and lymphopenia but survived without severe morbidity or histopathologic lesions. In monkeys, interstitial nephritis was the treatment-limiting toxicity and three of six monkeys treated with 45 or 30 mg/kg died, became moribund, or exhibited severe renal histopathologic lesions. One monkey treated with 45 mg/kg had degeneration of the testes. Survivors exhibited reversible toxicity and no histopathologic lesions. Treatment with doses as low as 7.5 mg/kg caused reversible neutropenia, lymphopenia, and anemia. The largest nontoxic dose for a single iv infusion was 3.12 mg/kg (62.40 mg/m2) for the dog and 3.75 mg/kg (45 mg/m2) for the monkey. These and earlier observations showed that methyl-CCNU had approximately one third the toxicity of CCNU. Methyl-CCNU also did not cause the delayed hepatic toxicity which is characteristic of CCNU treatment in the dog.
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PMID:Methyl-CCNU: preclinical toxicologic evaluation of a single iv infusion in dogs and monkeys. 82 19