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首页> 美国政府科技报告 >Phase 2 Report of Preclinical Lethality Studies in Mice, Pharmacokinetic Study in Dogs, and Toxicity Studies in Dogs and Rats of Pyrazine Diazohydroxide (NSC-361456)
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Phase 2 Report of Preclinical Lethality Studies in Mice, Pharmacokinetic Study in Dogs, and Toxicity Studies in Dogs and Rats of Pyrazine Diazohydroxide (NSC-361456)

机译：小鼠临床前致死率研究的第2阶段报告，犬的药代动力学研究以及吡嗪重氮氢氧化物（NsC-361456）的犬和大鼠的毒性研究

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The antineoplastic Pyrazine Diazohydroxide (PZDH, NSC-361456) was given intravenously to CD2F1 mice, beagle dogs, and Fischer 344 rats. Pharmacokinetics in dogs were dose-dependent with an initial half-life of 9-19 min and plasma clearance of 19-40 ml/min/kg. A single dose of 500 mg/sq m or higher was lethal to dogs while x2BW doses at 498 mg/sq m per dose caused no mortality in rats. The dog was more severely affected than the rat. Clinical observations of general malaise and body weight loss were noted in all three species and mild gastrointestinal toxicity and high body temperature were noted in dogs. Clinical pathologic and histopathologic data in dogs and rats indicated that bone marrow, lymphoid tissues, and testes were the target organs of toxicity. Males and females were similarly affected. Except for testicular atrophy, which worsened with time, reversibility was evident in surviving animals.

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