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Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice.
Proc Natl Acad Sci U S A. 1991 Sep 01; 88(17):7595-9.PN

Abstract

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.

Authors+Show Affiliations

Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1881900

Citation

Agrawal, S, et al. "Pharmacokinetics, Biodistribution, and Stability of Oligodeoxynucleotide Phosphorothioates in Mice." Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 17, 1991, pp. 7595-9.
Agrawal S, Temsamani J, Tang JY. Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc Natl Acad Sci U S A. 1991;88(17):7595-9.
Agrawal, S., Temsamani, J., & Tang, J. Y. (1991). Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proceedings of the National Academy of Sciences of the United States of America, 88(17), 7595-9.
Agrawal S, Temsamani J, Tang JY. Pharmacokinetics, Biodistribution, and Stability of Oligodeoxynucleotide Phosphorothioates in Mice. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7595-9. PubMed PMID: 1881900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. AU - Agrawal,S, AU - Temsamani,J, AU - Tang,J Y, PY - 1991/9/1/pubmed PY - 1991/9/1/medline PY - 1991/9/1/entrez SP - 7595 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 88 IS - 17 N2 - 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. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/1881900/Pharmacokinetics_biodistribution_and_stability_of_oligodeoxynucleotide_phosphorothioates_in_mice_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1881900 DB - PRIME DP - Unbound Medicine ER -