Complex Drug Interactions: Significance and Evaluation

  • Ping Zhao
  • Lei Zhang
  • Shiew-Mei Huang


Complex drug interactions that result from a multiplicity of factors (e.g., concomitant medications, organ dysfunction, genetic polymorphism of enzyme/transporter) may be accompanied by important clinical relevance. However, it is difficult to properly design and evaluate all possible complex drug interactions during drug development. In this chapter, we review the types of complex drug interactions and recent advances in studying complex drug interactions using modeling and simulation approaches. Challenges in the quantitative evaluation of complex drug interactions include (1) the need to understand metabolism/transport pathways and their interplay, (2) accurate assessment of key parameters (e.g., fractional clearance) at the enzyme/transporter level, and (3) knowledge in how altered physiological conditions (e.g., by disease states) affect drug disposition and response. Additional research will provide confidence in the use of modeling and simulation to guide clinical study design and generate data for the informative labeling and effective use of medications.


Drug Interaction PBPK Model Drug Interaction Potential Drug Interaction Study Organ Impairment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA

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