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Physiologically based pharmacokinetic (PBPK) modeling of RNAi therapeutics: Opportunities and challenges.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2021 Jul; Vol. 189, pp. 114468. Date of Electronic Publication: 2021 Feb 10. - Publication Year :
- 2021
-
Abstract
- Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool with many demonstrated applications in various phases of drug development and regulatory review. RNA interference (RNAi)-based therapeutics are a class of drugs that have unique pharmacokinetic properties and mechanisms of action. With an increasing number of RNAi therapeutics in the pipeline and reaching the market, there is a considerable amount of active research in this area requiring a multidisciplinary approach. The application of PBPK models for RNAi therapeutics is in its infancy and its utility to facilitate the development of this new class of drugs is yet to be fully evaluated. From this perspective, we briefly discuss some of the current computational modeling approaches used in support of efficient development and approval of RNAi therapeutics. Considerations for PBPK model development are highlighted both in a relative context between small molecules and large molecules such as monoclonal antibodies and as it applies to RNAi therapeutics. In addition, the prospects for drawing upon other recognized avenues of PBPK modeling and some of the foreseeable challenges in PBPK model development for these chemical modalities are briefly discussed. Finally, an exploration of the potential application of PBPK model development for RNAi therapeutics is provided. We hope these preliminary thoughts will help initiate a dialogue between scientists in the relevant sectors to examine the value of PBPK modeling for RNAi therapeutics. Such evaluations could help standardize the practice in the future and support appropriate guidance development for strengthening the RNAi therapeutics development program.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal genetics
Antibodies, Monoclonal metabolism
Drug Development trends
Humans
Oligonucleotides antagonists & inhibitors
Oligonucleotides genetics
Oligonucleotides metabolism
RNA Interference physiology
RNAi Therapeutics trends
Drug Development methods
Models, Biological
RNA Interference drug effects
RNAi Therapeutics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 189
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33577889
- Full Text :
- https://doi.org/10.1016/j.bcp.2021.114468