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. 1992 Jan 25;20(2):307–314. doi: 10.1093/nar/20.2.307

In vivo stability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides.

J G Zendegui 1, K M Vasquez 1, J H Tinsley 1, D J Kessler 1, M E Hogan 1
PMCID: PMC310371  PMID: 1741256

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.

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Selected References

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