In vivo stability and disposition of a self-stabilized oligodeoxynucleotide phosphorothioate in rats

R. Zhang, Z. Lu, X. Zhang, H. Zhao, Robert B Diasio, T. Liu, Z. Jiang, S. Agrawal

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The use of antisense oligonucleotides represents a novel, genetically based therapy. The biostability and pharmacokinetics of a 33-mer self- stabilized oligodeoxynucleotide with significant anti-HIV activity was determined in rats after intravenous administration of [35S]oligodeoxynucleotide. Plasma disappearance of the labeled oligodeoxynucleotide could be described by a two-compartment model, with half-lives of 0.54 and 41.44 h. The oligodeoxynucleotide in plasma remained mainly intact. Urinary excretion represented the major elimination pathway, with ~27% of the administered dose excreted within 24 h and 57% over 240 h. The majority of radioactivity in urine was attached to degradative products. Fecal excretion was a minor elimination pathway. A wide tissue distribution of the oligonucleotide was observed, with the majority of radioactivity in most tissues being intact. Compared with other linear oligonucleotide phosphorothioates, the self-stabilized oligonucleotide was more stable in vivo, which may be important in development of antisense oligonucleotides as therapeutic agents.

Original languageEnglish (US)
Pages (from-to)836-843
Number of pages8
JournalClinical Chemistry
Volume41
Issue number6
StatePublished - 1995
Externally publishedYes

Fingerprint

Oligodeoxyribonucleotides
Rats
Antisense Oligonucleotides
Radioactivity
Oligonucleotides
Phosphorothioate Oligonucleotides
Tissue
Plasmas
Pharmacokinetics
Tissue Distribution
Intravenous Administration
HIV
Urine
Therapeutics

Keywords

  • antisense oligonucleotides
  • biostability
  • feces
  • gene therapy
  • metabolism
  • pharmacokinetics
  • tissue distribution
  • urine

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Zhang, R., Lu, Z., Zhang, X., Zhao, H., Diasio, R. B., Liu, T., ... Agrawal, S. (1995). In vivo stability and disposition of a self-stabilized oligodeoxynucleotide phosphorothioate in rats. Clinical Chemistry, 41(6), 836-843.

In vivo stability and disposition of a self-stabilized oligodeoxynucleotide phosphorothioate in rats. / Zhang, R.; Lu, Z.; Zhang, X.; Zhao, H.; Diasio, Robert B; Liu, T.; Jiang, Z.; Agrawal, S.

In: Clinical Chemistry, Vol. 41, No. 6, 1995, p. 836-843.

Research output: Contribution to journalArticle

Zhang, R, Lu, Z, Zhang, X, Zhao, H, Diasio, RB, Liu, T, Jiang, Z & Agrawal, S 1995, 'In vivo stability and disposition of a self-stabilized oligodeoxynucleotide phosphorothioate in rats', Clinical Chemistry, vol. 41, no. 6, pp. 836-843.
Zhang, R. ; Lu, Z. ; Zhang, X. ; Zhao, H. ; Diasio, Robert B ; Liu, T. ; Jiang, Z. ; Agrawal, S. / In vivo stability and disposition of a self-stabilized oligodeoxynucleotide phosphorothioate in rats. In: Clinical Chemistry. 1995 ; Vol. 41, No. 6. pp. 836-843.
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