| Pharmacokinetics of a 14C-labeled phosphorothioate oligonucleotide, ISIS 2105, after intradermal administration to rats. | |
| | |
MedLine Citation:
|
PMID: 8169856 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
After intradermal administration of 3.7 mg/kg of 14C-labeled 5'-TTGCTTCCATCTTCCTCGTC-3' (14C-labeled ISIS 2105) to rats, a phosphorothioate oligodeoxynucleotide, absorption was rapid. Approximately 65% of the administered dose was absorbed within 1 hr after the dose and peak blood levels were achieved within 30 min. After the initial rapid phase of absorption, a slower absorption phase ensued that resulted in more than 95% of the dose being cleared from the injection site. Slow metabolism of 14C-labeled ISIS 2105 occurred at the injection site. The rate and characteristics of metabolism in the skin were similar to those observed in other tissues. Once absorbed, the pharmacokinetics, distribution and metabolism of 14C-labeled ISIS 2105 after intradermal administration were comparable to those after an i.v. dose. The distribution and terminal half-lives were 0.5 and 53 hr, respectively. Levels of 14C-labeled ISIS 2105 in the blood were found in the plasma and the drug distributed broadly to all peripheral tissues; the liver, renal cortex and bone marrow accumulated the highest levels of drug. The 14C-labeled ISIS 2105 was eliminated principally by metabolism. Approximately 50% of the dose was found in expired air and 15% and 5% were found in urine and feces, respectively. No intact oligonucleotide was found in urine or feces at any time. |
| | |
Authors:
|
P A Cossum; L Truong; S R Owens; P M Markham; J P Shea; S T Crooke |
Related Documents
:
|
6705136 - Repeated daunomycin administration in rats. pharmacokinetics and bone marrow toxicity. 1632106 - Disposition of minaprine in animals and in human extensive and limited debrisoquine hyd... 597816 - Pharmacokinetics of the absorption, distribution, and elimination of melphalan in the dog. 12214326 - The outstanding metabolic stability of a 14c-labeled beta-nonapeptide in rats--in vitro... 7900256 - Efficacy of oral moxidectin against benzimidazole-resistant isolates of gastrointestina... 8901676 - Inhibition of acute stent thrombosis under high-shear flow conditions by a nitric oxide... |
Publication Detail:
|
Type: Comparative Study; Journal Article |
Journal Detail:
|
Title: The Journal of pharmacology and experimental therapeutics Volume: 269 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1994 Apr |
Date Detail:
|
Created Date: 1994-06-02 Completed Date: 1994-06-02 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 89-94 Citation Subset: IM |
Affiliation:
|
Triplex Pharmaceuticals Corporation, The Woodlands, Texas. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Absorption Animals Antiviral Agents / blood, metabolism, pharmacokinetics* Base Sequence Carbon Radioisotopes / diagnostic use Chromatography, High Pressure Liquid Feces / chemistry Female Injections, Intradermal Molecular Sequence Data Rats Skin / metabolism Thionucleotides / classification, metabolism, pharmacokinetics* Tissue Distribution |
| Chemical | |
Reg. No./Substance:
|
0/Antiviral Agents; 0/Carbon Radioisotopes; 0/Thionucleotides; 138330-98-0/afovirsen sodium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Vascular reactivity to angiotensin II is selectively enhanced in the kidneys of spontaneously hypert...
Next Document: Adaptation of the N-methyl-D-aspartate receptor complex following chronic antidepressant treatments.