PMID: 8597088DOI: 10.1016/0378-4274(95)03572-9Dec 1, 1995Paper
Pharmacology and toxicology of phosphorothioate oligonucleotides in the mouse, rat, monkey and man
Toxicology Letters
P IversenH K Tewary
Abstract
Phosphorothioate oligonucleotides (PS-ODN) designed to temporarily modulate selected gene expression have made the journey from bench top to beside 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.
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