Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice.

AUTOR(ES)

Agrawal, S

RESUMO

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

Documentos Relacionados

• Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity
• Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H.
• Systemic gene therapy: biodistribution and long-term expression of a transgene in mice.
• Pharmacokinetics of ribavirin aerosol in mice.
• Antimalarial activities of oligodeoxynucleotide phosphorothioates in chloroquine-resistant Plasmodium falciparum.