Thank you, Simone for the paper. Great share, this study nails PBPK framework for a lymphatic-first, long-acting nanoparticle (Class II) and bridges preclinical species datasets to early clinical planning. Happy to learn about such translational work.
We still lack robust in-vitro surrogates for Class II behavior, so curious how scientific communities are approaching in-vitro surrogates for Class II today?
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Pankajini Mallick Ph.D.
Sr. Principal Scientist, DMPK, PK/PD
San Diego CA
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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Original Message:
Sent: 08-27-2025 11:09
From: Simone Perazzolo
Subject: New AAPS Journal article of possible community Interest | Optimization of In Vitro CYP3A4 TDI Assay Conditions
You can check out this paper from us - strongly mechanistic with rationale of parameter selection (especially in the supplementary). To your question, DDI is extremely time-dependent.
https://pubmed.ncbi.nlm.nih.gov/38382809/
Hope it helps- regards
simone
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Simone Perazzolo
Scientist
University of Washington
Seattle WA
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
Original Message:
Sent: 08-26-2025 05:18
From: Pankajini Mallick
Subject: New AAPS Journal article of possible community Interest | Optimization of In Vitro CYP3A4 TDI Assay Conditions
Why it matters: Time-dependent inhibition (TDI) of CYP3A4 is a leading cause of clinical drug–drug interactions (DDIs). This study refines assay conditions to improve reproducibility and delivers robust kinetic parameters (e.g., kinact, KI, KI,u) that translate into clearer risk assessments with both mechanistic static metrics and PBPK (dynamic) models.
Read the full article at: Optimization of In Vitro CYP3A4 TDI Assay Conditions and Use of Derived Parameters for Clinical DDI Risk Assessment Using Static and Dynamic Models - The AAPS Journal
| SpringerLink |
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| Optimization of In Vitro CYP3A4 TDI Assay Conditions and Use of Derived Parameters for Clinical DDI Risk Assessment Using Static and Dynamic Models - The AAPS Journal |
| Cytochrome P450 3A4 (CYP3A4) is a key target for time-dependent inhibition (TDI) assessment during drug development. However, translating in vitro TDI data to in vivo drug-drug interaction (DDI) risk remains challenging due to the acknowledged overestimation when incorporating in vitro kinetics in predictive models. |
| View this on SpringerLink > |
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#CYP3A4 #TDI #DrugDrugInteractions
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Pankajini Mallick Ph.D.
Sr. Principal Scientist, DMPK, PK/PD
San Diego CA
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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