Drug Combinations: Tests and Analysis with Isoboles

Ronald J. Tallarida1

1 Temple University School of Medicine, Philadelphia, Pennsylvania
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 9.19
DOI:  10.1002/0471141755.ph0919s72
Online Posting Date:  March, 2016
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Described in this unit are experimental and computational methods to detect and classify drug interactions. In most cases, this relates to two drugs or compounds with overtly similar effects, e.g., two analgesics or two anti‐hypertensives. From the dose‐response data of the individual drugs, it is possible to generate a curve, the isobole, which defines all dose combinations that are expected to yield a specified effect. The theory underlying the isobole involves the calculation of doses of drug A that are effectively equivalent to doses of drug B with that equivalence determining whether the isobole is linear or nonlinear. In either case, the isobole allows for a comparison with actual combination effects making it possible to determine whether the interaction is synergistic, additive, or sub‐additive. Actual as well as illustrative data are employed to demonstrate experimental design and data analysis. © 2016 by John Wiley & Sons, Inc.

Keywords: drug synergism; additivity; sub‐additivity

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Table of Contents

  • Introduction
  • Experimental Steps
  • Curved Isobole
  • Site‐Site Analysis
  • Opposite Effects
  • Summary and Discussion
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

Literature Cited
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