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

页码：425 / 430

页数：6

共 40 条

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