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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

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Published on: January 31, 2022

Reassessing models of hepatic extraction.

D Ridgway1, J A Tuszynski, Y K Tam

  • 1Kinetana Group Inc., 9650 - 20 Ave., Edmonton, AB T6N 1G1.

Journal of Biological Physics
|January 25, 2013
PubMed
Summary
This summary is machine-generated.

Comparing mathematical models for liver drug clearance, this study found dispersion and distributed tube models offer improved in vitro-in vivo correlation over the well-stirred model for high clearance drugs.

Keywords:
in vivo-in vitro correlationsmulti-compartment modelspharmacokinetics

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Area of Science:

  • Pharmacokinetics
  • Mathematical Modeling
  • Drug Metabolism

Background:

  • In vitro-in vivo correlation (IVIVC) is crucial for predicting drug behavior.
  • Accurate mathematical models are needed to improve IVIVC for drug development.
  • Existing models, like the well-stirred model, may have limitations.

Purpose of the Study:

  • To compare the performance of different mathematical models for liver drug clearance.
  • To evaluate the accuracy of the well-stirred, distributed tubes, and dispersion models in IVIVC.
  • To identify optimal models for predicting in vivo drug clearance from in vitro data.

Main Methods:

  • Reanalyzed existing drug data from Houston reviews.
  • Fitted well-stirred, distributed tubes, and dispersion models to in vitro and in vivo intrinsic clearance data.
  • Utilized data from microsomal and hepatocyte experiments.

Main Results:

  • The distributed tubes and dispersion models showed reduced residuals compared to the well-stirred model.
  • Neither the distributed tubes nor the dispersion model was clearly superior to the other.
  • Drug-specific factors significantly impact the quality of IVIVC.

Conclusions:

  • Improved IVIVC for high clearance drugs is achievable using dispersion or distributed tube models.
  • The choice of model impacts the reliability of predicting in vivo drug performance.
  • Further experimental validation is necessary to confirm IVIVC model performance.