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Antisense oligonucleotide pharmacokinetics and metabolism

Antisense oligonucleotide pharmacokinetics and metabolism Background: The use of oligonucleotides as therapeutic agents has elicited a great deal of interest. Basic understanding and evaluation of the pharmacokinetic properties of oligonucleotides is foundational to their appropriate design and application. Objective: To review the primary pharmacokinetic properties that drive successful use and delivery of oligonucleotides. Methods: The primary data set available in the published literature for summarizing the pharmacokinetic properties of oligonucleotides exists for single strand phosphorothioate antisense oligonucleotides and their chimeric chemical modifications (second generation). Where possible, data from other classes of compounds are contrasted with this base class. Results/conclusion: Although there are several different classes of oligonucleotides being developed as therapeutic agents, their pharmacokinetic properties by class are primarily a function of their backbone chemistry and the resulting chemical relationship to biological stability and plasma protein binding properties. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Expert Opinion on Drug Metabolism & Toxicology Taylor & Francis

Antisense oligonucleotide pharmacokinetics and metabolism

12 pages

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References (76)

Publisher
Taylor & Francis
Copyright
©© Informa UK Ltd
ISSN
1744-7607
eISSN
1742-5255
DOI
10.1517/17425250902877680
Publisher site
See Article on Publisher Site

Abstract

Background: The use of oligonucleotides as therapeutic agents has elicited a great deal of interest. Basic understanding and evaluation of the pharmacokinetic properties of oligonucleotides is foundational to their appropriate design and application. Objective: To review the primary pharmacokinetic properties that drive successful use and delivery of oligonucleotides. Methods: The primary data set available in the published literature for summarizing the pharmacokinetic properties of oligonucleotides exists for single strand phosphorothioate antisense oligonucleotides and their chimeric chemical modifications (second generation). Where possible, data from other classes of compounds are contrasted with this base class. Results/conclusion: Although there are several different classes of oligonucleotides being developed as therapeutic agents, their pharmacokinetic properties by class are primarily a function of their backbone chemistry and the resulting chemical relationship to biological stability and plasma protein binding properties.

Journal

Expert Opinion on Drug Metabolism & ToxicologyTaylor & Francis

Published: Apr 1, 2009

Keywords: ADME; mRNA; oligoneucleotide; pharmacokinetics

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