Pharmacology and toxicology of phosphorothioate oligonucleotides in the mouse, rat, monkey and man

被引：30
作者：
Iversen, PL [1 ]
Copple, BL [1 ]
Tewary, HK [1 ]
机构：
[1] UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC,DEPT PHARMACEUT SCI,OMAHA,NE 68198
来源：
TOXICOLOGY LETTERS | 1995年 / 82-3卷
关键词：
phosphorothioate oligonucleotides; preclinical pharmacology; DNA damage; p53; mRNA; gene-specific therapeutics;
D O I：
10.1016/0378-4274(95)03572-9
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
Phosphorothioate oligonucleotides (PS-ODN) designed to temporarily modulate selected gene expression have made the journey from bench top to bedside in a remarkably short period of time. A PS-ODN with sequence complementary to the p53 mRNA was administered to mice (4 mg/kg subcutaneously), rats (3-300 mg/kg intravenously), monkeys (intravenous infusions for up to 15 days) and humans (up to 0.25 mg/kg/h intravenous infusions for 10 days). These studies demonstrate the PS-ODN provides feasible pharmacokinetic parameters and minimal toxicity.
引用
收藏
页码：425 / 430
页数：6
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