Tags

Type your tag names separated by a space and hit enter

In vivo stability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides.
Nucleic Acids Res. 1992 Jan 25; 20(2):307-14.NA

Abstract

Development of oligonucleotide derivatives as therapeutic agents requires an understanding of their pharmacokinetic behavior. The in vivo disposition and stability of a prototype of such compounds are reported here. The compound studied, a relatively G-rich 38 base 3' phosphopropyl amine oligonucleotide (TFO-1), was cleared from the circulation with a half-life of approximately 10 minutes, displaying distribution kinetics consistent with a two compartment model. TFO-1 was also readily absorbed into circulation from the peritoneal cavity. All tissues examined except brain accumulated the compound reaching concentrations calculated to be in the micromolar range. TFO-1 was found to be stable in circulation and in tissues in that a large fraction of intact material was detected 8 hours after injection, as assessed by gel electrophoresis. Approximately 20-30% of the injected dose was excreted in the urine over an 8 hour period. These results suggest that G-rich oligonucleotides, minimally modified at the 3' end, are relatively stable in vivo and have distribution kinetics favorable to use as therapeutic agents.

Authors+Show Affiliations

Triplex Pharmaceutical Corporation, The Woodlands, TX 77380.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1741256

Citation

Zendegui, J G., et al. "In Vivo Stability and Kinetics of Absorption and Disposition of 3' Phosphopropyl Amine Oligonucleotides." Nucleic Acids Research, vol. 20, no. 2, 1992, pp. 307-14.
Zendegui JG, Vasquez KM, Tinsley JH, et al. In vivo stability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides. Nucleic Acids Res. 1992;20(2):307-14.
Zendegui, J. G., Vasquez, K. M., Tinsley, J. H., Kessler, D. J., & Hogan, M. E. (1992). In vivo stability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides. Nucleic Acids Research, 20(2), 307-14.
Zendegui JG, et al. In Vivo Stability and Kinetics of Absorption and Disposition of 3' Phosphopropyl Amine Oligonucleotides. Nucleic Acids Res. 1992 Jan 25;20(2):307-14. PubMed PMID: 1741256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo stability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides. AU - Zendegui,J G, AU - Vasquez,K M, AU - Tinsley,J H, AU - Kessler,D J, AU - Hogan,M E, PY - 1992/1/25/pubmed PY - 1992/1/25/medline PY - 1992/1/25/entrez SP - 307 EP - 14 JF - Nucleic acids research JO - Nucleic Acids Res VL - 20 IS - 2 N2 - Development of oligonucleotide derivatives as therapeutic agents requires an understanding of their pharmacokinetic behavior. The in vivo disposition and stability of a prototype of such compounds are reported here. The compound studied, a relatively G-rich 38 base 3' phosphopropyl amine oligonucleotide (TFO-1), was cleared from the circulation with a half-life of approximately 10 minutes, displaying distribution kinetics consistent with a two compartment model. TFO-1 was also readily absorbed into circulation from the peritoneal cavity. All tissues examined except brain accumulated the compound reaching concentrations calculated to be in the micromolar range. TFO-1 was found to be stable in circulation and in tissues in that a large fraction of intact material was detected 8 hours after injection, as assessed by gel electrophoresis. Approximately 20-30% of the injected dose was excreted in the urine over an 8 hour period. These results suggest that G-rich oligonucleotides, minimally modified at the 3' end, are relatively stable in vivo and have distribution kinetics favorable to use as therapeutic agents. SN - 0305-1048 UR - https://www.unboundmedicine.com/medline/citation/1741256/In_vivo_stability_and_kinetics_of_absorption_and_disposition_of_3'_phosphopropyl_amine_oligonucleotides_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/20.2.307 DB - PRIME DP - Unbound Medicine ER -