Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice

摘要: Abstract We describe preliminary studies of the pharmacokinetics, biodistribution, and excretion an oligodeoxy-nucleotide phosphorothioate ([S]oligonucleotide) in mice. After either intravenous or intraperitoneal administration a single dose (30 mg/kg body weight), [S]oligonucleotide (35S-labeled at each internucleotide linkage) was found most tissues for up to 48 hr. About 30% excreted urine within 24 hr, irrespective mode administration; be extensively degraded. In plasma, stomach, heart, intestine, degraded by only 15%, whereas kidney liver degradation about 50% The surprising observation made that chain length extension administered occurred kidney, liver, intestine. These results provide initial definition parameters pharmaceutical development antisense oligonucleotides.