Pharmacokinetics, Pharmacodynamics, & Drug Metabolism Community

Hi everyone,

I came across an interesting paper recently published in the AAPS Journal that I wanted to share.

Leveraging Buprenorphine and Halofantrine as Tool Molecules to Develop a Novel Semi-Physiologically based Pharmacokinetic Model Accounting for Gastro-Intestinal Lymphatic Absorption and Enabling Cross-Species Translation | The AAPS Journal

This is a great paper that sheds light on intestinal lymphatic absorption and introduces a novel PBPK modeling framework that can be extended to other lipophilic compounds or lipid-based formulations for simulating systemic exposure. The model incorporates chylomicron-mediated drug transport and cross-species translation, making it a valuable tool for oral drug development.

I think it would be more powerful if this model could also incorporate metabolite prediction to better capture compound-specific metabolism.

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Yi-Hua Chiang
Ph.D. Student
University of Florida
Gainesville FL
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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Thank You, Yi-Hua for sharing this paper and your thoughts. This work advances GI-lymphatic absorption from concept to a semi-physiologic framework.

I agree that, for prodrug strategies, cross-species scaling must balance chylomicron extraction (CE) versus enterocyte/gut metabolism to avoid over- or under-predicting human F. I'm curious how teams quantify food effects in PBPK for lymphotropic drugs, e.g fixed scalars, mechanistic lipid-digestion submodels, or empirical fits? And with sparse human anchors for CM formation/turnover and CE–metabolism competition, how to handle uncertainty?

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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: 04-17-2025 17:13
From: Yi-Hua Chiang
Subject: GI-Lymph-PBPK Model for Simulating Lipophilic Drug Absorption

Hi everyone,

I came across an interesting paper recently published in the AAPS Journal that I wanted to share.

Leveraging Buprenorphine and Halofantrine as Tool Molecules to Develop a Novel Semi-Physiologically based Pharmacokinetic Model Accounting for Gastro-Intestinal Lymphatic Absorption and Enabling Cross-Species Translation | The AAPS Journal

This is a great paper that sheds light on intestinal lymphatic absorption and introduces a novel PBPK modeling framework that can be extended to other lipophilic compounds or lipid-based formulations for simulating systemic exposure. The model incorporates chylomicron-mediated drug transport and cross-species translation, making it a valuable tool for oral drug development.

I think it would be more powerful if this model could also incorporate metabolite prediction to better capture compound-specific metabolism.

------------------------------
Yi-Hua Chiang
Ph.D. Student
University of Florida
Gainesville FL
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
------------------------------