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Pharmacokinetics, biodistribution, and stability of capped oligodeoxynucleotide phosphorothioates in mice.
Antisense Res Dev. 1993 Fall; 3(3):277-84.AR

Abstract

Several end-modified oligodeoxynucleotide phosphorothioates (S-oligonucleotides) were studied for their pharmacokinetics, biodistribution, excretion, and metabolic stability in vivo after intravenous administration in mice. The overall tissue distribution and excretion patterns of these S-oligonucleotides were found to be independent of 5' or 3' end modification studied. However, the 3' end modification proved to be of considerable importance with respect to metabolic stability of the oligonucleotide. In the case of uncapped and 5'-capped S-oligonucleotide, only 50% of intact oligonucleotide was recovered out of the total bioavailable concentration in liver and kidney. In contrast, in the case of 3'-capped oligonucleotides almost all bioavailable concentrations of 3'-capped oligonucleotide was found to be intact in kidney and liver at 24 hr after administration. These results demonstrate that superior pharmaceutical potential can be created by 3'-end modification of oligonucleotide phosphorothioates.

Authors+Show Affiliations

Hybridon, Inc., Worcester, Massachusetts 01605.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8286928

Citation

Temsamani, J, et al. "Pharmacokinetics, Biodistribution, and Stability of Capped Oligodeoxynucleotide Phosphorothioates in Mice." Antisense Research and Development, vol. 3, no. 3, 1993, pp. 277-84.
Temsamani J, Tang JY, Padmapriya A, et al. Pharmacokinetics, biodistribution, and stability of capped oligodeoxynucleotide phosphorothioates in mice. Antisense Res Dev. 1993;3(3):277-84.
Temsamani, J., Tang, J. Y., Padmapriya, A., Kubert, M., & Agrawal, S. (1993). Pharmacokinetics, biodistribution, and stability of capped oligodeoxynucleotide phosphorothioates in mice. Antisense Research and Development, 3(3), 277-84.
Temsamani J, et al. Pharmacokinetics, Biodistribution, and Stability of Capped Oligodeoxynucleotide Phosphorothioates in Mice. Antisense Res Dev. 1993;3(3):277-84. PubMed PMID: 8286928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics, biodistribution, and stability of capped oligodeoxynucleotide phosphorothioates in mice. AU - Temsamani,J, AU - Tang,J Y, AU - Padmapriya,A, AU - Kubert,M, AU - Agrawal,S, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - 277 EP - 84 JF - Antisense research and development JO - Antisense Res Dev VL - 3 IS - 3 N2 - Several end-modified oligodeoxynucleotide phosphorothioates (S-oligonucleotides) were studied for their pharmacokinetics, biodistribution, excretion, and metabolic stability in vivo after intravenous administration in mice. The overall tissue distribution and excretion patterns of these S-oligonucleotides were found to be independent of 5' or 3' end modification studied. However, the 3' end modification proved to be of considerable importance with respect to metabolic stability of the oligonucleotide. In the case of uncapped and 5'-capped S-oligonucleotide, only 50% of intact oligonucleotide was recovered out of the total bioavailable concentration in liver and kidney. In contrast, in the case of 3'-capped oligonucleotides almost all bioavailable concentrations of 3'-capped oligonucleotide was found to be intact in kidney and liver at 24 hr after administration. These results demonstrate that superior pharmaceutical potential can be created by 3'-end modification of oligonucleotide phosphorothioates. SN - 1050-5261 UR - https://www.unboundmedicine.com/medline/citation/8286928/Pharmacokinetics_biodistribution_and_stability_of_capped_oligodeoxynucleotide_phosphorothioates_in_mice_ L2 - https://www.lens.org/lens/search/patent/list?q=citation_id:8286928 DB - PRIME DP - Unbound Medicine ER -