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Tytuł pozycji:

Physiologically based pharmacokinetic (PBPK) modeling of RNAi therapeutics: Opportunities and challenges.

Tytuł :
Physiologically based pharmacokinetic (PBPK) modeling of RNAi therapeutics: Opportunities and challenges.
Autorzy :
Fairman K; Division of Biochemical Toxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079, USA.
Li M; Division of Biochemical Toxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079, USA.
Ning B; Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079, USA.
Lumen A; Division of Biochemical Toxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: .
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Źródło :
Biochemical pharmacology [Biochem Pharmacol] 2021 Jul; Vol. 189, pp. 114468. Date of Electronic Publication: 2021 Feb 10.
Typ publikacji :
Journal Article; Research Support, N.I.H., Extramural; Review
Język :
English
Imprint Name(s) :
Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
MeSH Terms :
Models, Biological*
Drug Development/*methods
RNA Interference/*drug effects
RNAi Therapeutics/*methods
Animals ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/metabolism ; Drug Development/trends ; Humans ; Oligonucleotides/antagonists & inhibitors ; Oligonucleotides/genetics ; Oligonucleotides/metabolism ; RNA Interference/physiology ; RNAi Therapeutics/trends
Contributed Indexing :
Keywords: Modeling*; Oligonucleotides*; PBPK*; RNA therapeutics*; RNAi*; siRNA*
Substance Nomenclature :
0 (Antibodies, Monoclonal)
0 (Oligonucleotides)
Entry Date(s) :
Date Created: 20210212 Date Completed: 20210913 Latest Revision: 20210913
Update Code :
20210920
DOI :
10.1016/j.bcp.2021.114468
PMID :
33577889
Czasopismo naukowe
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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Comment in: Biochem Pharmacol. 2021 Jul;189:114567. (PMID: 33865832)

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