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A foundation for reference models for drug combinations with an application to Loewe's reference model
Wim De Mulder1, Martin Kuiper2
1Department of Biology, NTNU, Realfagbygget, Trondheim, Norway. wim.demulder@kuleuven.be.
BMC Bioinformatics
|October 16, 2020
Summary
This study provides a fundamental basis for Loewe
Area of Science:
- Pharmacology
- Mathematical Biology
- Drug Combinations
Background:
- Synergistic drug combinations are widely used in clinical practice.
- Defining drug non-interaction is crucial for predicting combination effects.
- Loewe's reference model is a long-standing, intuitive model for drug non-interaction.
Purpose of the Study:
- To derive Loewe's reference model from more fundamental principles.
- To introduce novel concepts of complementary and equivalent doses.
- To propose a general non-interaction principle for drug combinations.
Main Methods:
- Introduction of the concept of complementary dose.
- Reformulation of equivalent dose for broader applicability.
- Development of a general non-interaction principle based on dose interplay.
Main Results:
- Loewe's reference model can be derived from fundamental principles.
- A new, general non-interaction principle is established.
- This principle links complementary and equivalent doses.
Conclusions:
- The study enhances understanding of Loewe's reference model.
- A general non-interaction principle is presented, independent of specific dose-response curves.
- This work offers a more robust theoretical framework for analyzing drug interactions.
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