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Nonlinear Pharmacokinetics: Causes of Nonlinearity01:22

Nonlinear Pharmacokinetics: Causes of Nonlinearity

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Nonlinearity in drug pharmacokinetics is caused by various factors influencing how a drug is absorbed, distributed, metabolized, and excreted. Understanding these nonlinear processes is crucial for predicting drug behavior in the body and optimizing drug dosing regimens.
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Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
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Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter? 
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Development of an Individual-Tree Basal Area Increment Model using a Linear Mixed-Effects Approach
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Nonlinear Mixed-Effects Model Development and Simulation Using nlmixr and Related R Open-Source Packages.

Matthew Fidler1, Justin J Wilkins2, Richard Hooijmaijers3

  • 1Novartis Pharmaceuticals Corporation, Fort Worth, Texas, USA.

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nlmixr is a free R package for nonlinear pharmacokinetic (PK) and pharmacodynamic (PD) mixed-effects modeling. It offers an open-source alternative to commercial software for complex PK/PD and systems pharmacology analyses.

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Area of Science:

  • Pharmacometrics
  • Computational Biology
  • Pharmacology

Background:

  • Nonlinear mixed-effects modeling is crucial for pharmacokinetic (PK) and pharmacodynamic (PD) analysis.
  • Commercial software packages are widely used but can be costly.
  • There is a need for accessible, open-source alternatives in PK/PD modeling.

Purpose of the Study:

  • Introduce nlmixr, a new free and open-source R package.
  • To provide a credible alternative to commercial software for mixed-effects modeling.
  • To support fitting of various PK, PD, joint PK-PD, and quantitative systems pharmacology models.

Main Methods:

  • Developed as an R package utilizing the R programming language.
  • Capable of fitting traditional compartmental PK models.
  • Supports complex models implemented using ordinary differential equations (ODEs).

Main Results:

  • nlmixr is a functional R package for nonlinear mixed-effects modeling.
  • It accommodates diverse model types, including compartmental and ODE-based models.
  • Demonstrates potential as a viable alternative to established commercial software.

Conclusions:

  • nlmixr offers a powerful, free, and open-source solution for PK/PD and systems pharmacology modeling.
  • The package supports a range of complex modeling approaches.
  • It aims to enhance accessibility and credibility in the field of mixed-effects modeling.