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Published on: September 21, 2017
The disposition (ADME) of antisense oligonucleotides
1Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. bdvorchik@email.msn.com
Current Opinion in Molecular Therapeutics
|March 16, 2001
Summary
Antisense oligonucleotides (ASOs) show therapeutic promise but require sufficient delivery for efficacy. Understanding ASO pharmacokinetics, including absorption, distribution, metabolism, and elimination (ADME), is crucial for developing effective treatments.
Area of Science:
- Pharmacology
- Molecular Biology
- Drug Development
Background:
- Antisense oligonucleotides (ASOs) are promising therapeutic agents targeting specific gene products.
- Therapeutic efficacy of ASOs depends on reaching target sites in sufficient concentrations.
- Pharmacokinetics (PK), encompassing absorption, distribution, metabolism, and elimination (ADME), is vital for drug development.
Purpose of the Study:
- To review the pharmacokinetics of antisense oligonucleotides.
- To highlight mechanisms of oligonucleotide accumulation in tissues and cells.
- To identify limitations and guide the development of effective ASO therapeutics.
Main Methods:
- Review of non-clinical and clinical studies on ASO pharmacokinetics.
- Analysis of published contributions from 1997 to 2000.
- Presentation of underlying ADME principles for oligonucleotides.
Main Results:
- ASO efficacy is contingent upon achieving adequate concentrations at the site of action.
- Understanding ASO ADME is critical for assessing therapeutic potential and limitations.
- Accumulation mechanisms in tissues and cells are key to ASO pharmacokinetics.
Conclusions:
- Pharmacokinetic understanding is essential for advancing antisense oligonucleotide therapeutics.
- Further research into ASO tissue and cellular accumulation is needed.
- This review consolidates knowledge on ASO pharmacokinetics to inform future development.
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