Pharmacology and toxicology of phosphorothioate oligonucleotides in the mouse, rat, monkey and man.
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.
Iversen
P L
PL
Department of Pharmacology, Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Copple
B L
BL
Tewary
H K
HK
D000818:Animals; D001483:Base Sequence; D016158:Genes, p53; D006207:Half-Life; D000882:Haplorhini; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D013873:Thionucleotides / Q000493:pharmacokinetics* / Q000633:toxicity
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides