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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Citations

Jan 26, 1999·Antisense & Nucleic Acid Drug Development·Q ZhaoS Agrawal
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