[抗肿瘤铂(II)和铂(IV)配位化合物对实验室啮齿动物的急性和亚急性毒性]。

Archiv fur Geschwulstforschung Pub Date : 1989-01-01
A Härtl, J Güttner, U Horn, F Jelinek, U Stöckel, H P Schröer, H Hoffmann
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引用次数: 0

摘要

经单次静脉注射顺式二胺-铂(II)-乳酸顺式二胺-铂(II)-乳酸,L顺式二胺-铂(II)-dilactate反式二羟基顺式二氯二胺-铂(IV),小鼠的LD50值在80 ~ 130 mg/kg之间,大鼠的LD50值在22 ~ 45 mg/kg之间。cis-DDP的LD50分别为17 mg/kg和6.6 mg/kg。同样,当连续5天每天服用时,发现这些化合物的毒性比标准的顺式ddp低约3至5倍。由于肾脏、骨髓、淋巴组织和肠道已被证明是主要的靶器官,Pt(II)-复合物的毒性作用谱似乎与顺式ddp相似。此外,Pt(IV)化合物已被发现对胰腺、肝脏和唾液腺有毒。在抗肿瘤活性方面,与顺式ddp相比,可溶性乳酸含量较高的顺式ddp的治疗指数较低。
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[Acute and subacute toxicity of antineoplastic Pt(II) and Pt(IV) coordination compounds in laboratory rodents].

After single i.v. administration of cis-diammine-platinum(II)-lactate cis-diammine-platinum(II)-lactate, L cis-diammine-platinum(II)-dilactate trans-dihydroxy-cis-dichlorodiammine-platinum(IV), the LD50 values have been calculated to range between 80 and 130 mg/kg in mice, and between 22 and 45 mg/kg in rats. The LD50 of cis-DDP amounted to 17 mg/kg and 6.6 mg/kg, respectively. Likewise, the compounds have been found to be about 3 to 5 times less toxic than the standard cis-DDP when administered daily for 5 consecutive days. Since the kidneys, the bone marrow, the lymphatic tissue and the intestinal tract have been proved to be the main target organs, the profile of the toxic action of the Pt(II)-complexes seems to be similar to that of cis-DDP. Additionally, the Pt(IV) compound has been found to be toxic to the pancreas, the liver and the salivary glands. With regard to the antineoplastic activity the more soluble lactates of cis-DDP showed a smaller therapeutic index compared to cis-DDP.

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