Hi,
Please check out this latest publication in the AAPS Journal that highlights the impact of pharmacological target-mediated low plasma exposure in lead compound selection in drug discovery using the mPBPK approach.
Xu M, Sun D, An G. Exploring the Impact of Pharmacological Target-Mediated Low Plasma Exposure in Lead Compound Selection in Drug Discovery - A Modeling Approach. AAPS J. 2024 Oct 28;26(6):112. doi: 10.1208/s12248-024-00979-7. PMID: 39467882.
https://pubmed.ncbi.nlm.nih.gov/39467882/
This paper discusses a potential cause of low success rates in drug development: target-mediated low plasma exposure. This occurs when a drug binds strongly to its target in tissues, leading to low plasma concentrations and potentially misleading pharmacokinetic (PK) profiles.
The authors propose using a minimal physiologically-based pharmacokinetic (mPBPK) model to evaluate drug distribution and predict the impact of target binding on plasma exposure. This model can help identify compounds with high target affinity that may be overlooked due to low plasma concentrations.
The abstract highlights the importance of considering target-mediated effects during lead compound selection and suggests that traditional PK criteria may not be sufficient for identifying optimal drug candidates.
Sincerely,
Saima Subhani
Scientist I,
Simulations Plus. Inc
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Saima Subhani
Scientist
Simulations-Plus
Lansdale PA
[email protected]Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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