Document 0845
 DOCN  M9590845
 TI    In vivo stability and disposition of a self-stabilized
       oligodeoxynucleotide phosphorothioate in rats.
 DT    9509
 AU    Zhang R; Lu Z; Zhang X; Zhao H; Diasio RB; Liu T; Jiang Z; Agrawal S;
       Department of Pharmacology and Toxicology, University of Alabama; at
       Birmingham 35294, USA.
 SO    Clin Chem. 1995 Jun;41(6 Pt 1):836-43. Unique Identifier : AIDSLINE
       MED/95285567
 AB    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 approximately 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.
 DE    Animal  Base Sequence  Drug Stability  Feces/CHEMISTRY  HIV/DRUG EFFECTS
       Kinetics  Male  Molecular Sequence Data  Oligonucleotides,
       Antisense/CHEMISTRY/PHARMACOLOGY/  *PHARMACOKINETICS  Rats  Rats,
       Sprague-Dawley  Thionucleotides/CHEMISTRY/PHARMACOLOGY/*PHARMACOKINETICS
       Tissue Distribution  Urine/CHEMISTRY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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