Pharmacodynamic Drug–Drug Interactions

  • Ming ZhengEmail author
Living reference work entry


Concomitant medications with similar or opposite pharmacological effects can cause pharmacodynamic drug interactions. Pharmacodynamic interactions generally fall into three categories: additive, antagonistic and synergistic. This chapter describes the commonly used empirical methodologies to evaluate pharmacodynamic interactions. Due to knowledge and data gaps in the systems involved, pharmacodynamic interactions are difficult to predict. Quantitative systems pharmacology models are emerging recently as promising approaches that integrate knowledge from multiple disciplines including drug pharmacology, systems biology, physiology, mathematics and biochemistry. Readers are referred to other sources for more detailed discussions on such novel methodologies.


  1. Abernethy DR, Altman RB, Brouwer KLR et al (2011) Quantitative and systems pharmacology in the post-genomic era: new approaches to discovering drugs and understanding therapeutic mechanisms. An NIH White Paper by the QSP Workshop Group. October, 2011Google Scholar
  2. Allard B, Aspeslagh S, Garaud S et al (2018) Immuno-oncology-101: overview of major concepts and translational perspectives. Semin Cancer Biol.
  3. Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58Google Scholar
  4. Chou (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58:621–681CrossRefPubMedGoogle Scholar
  5. CURRENT–OASIS 7 Investigators (2010) Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 363:930–942CrossRefGoogle Scholar
  6. EMA (2012) Guideline on the investigation of drug interactionsGoogle Scholar
  7. FDA (2017) Guidance for industry, in vitro metabolism- and transporter-mediated drug-drug interaction studiesGoogle Scholar
  8. Gadkar K, Kirouac D, Parrott N et al (2016) Quantitative systems pharmacology: a promising approach for translational pharmacology. Drug Discov Today Technol 21–22:57–65CrossRefPubMedGoogle Scholar
  9. Gibaldi M, Perrier D (1982) Kinetics of pharmacologic response. In: pharmacokinetics, 2nd edn. Marcel Dekker, New York, p 222Google Scholar
  10. Jones HM, Chen Y, Gibson C et al (2015) Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective. Clin Pharmacol Ther 97(3):247–262CrossRefPubMedGoogle Scholar
  11. Leil TA, Ermakov S (2015) Editorial: the emerging discipline of quantitative systems pharmacology. Front Pharmacol 30(6):129Google Scholar
  12. Montgomery AA, Peters TJ, Little P (2003) Design, analysis and presentation of factorial randomized controlled trials. BMC Med Res Methodol 24(3):26CrossRefGoogle Scholar
  13. Pandis N, Walsh T, Polychronopoulou A et al (2014) Factorial designs: an overview with applications to orthodontic clinical trials. Eur J Orthod 36(3):314–320CrossRefPubMedGoogle Scholar
  14. Pocock SJ, Clayton TC, Stone GW (2015) Challenging issues in clinical trial design. J Am Coll Cardiol 66(25):2886–2898CrossRefPubMedGoogle Scholar
  15. Schild HO (1957) Drug antagonism and pA2. Pharmacol Rev 9:242–246PubMedGoogle Scholar
  16. Tallarida RJ (2006) An overview of drug combination analysis with isobolograms. J Pharmacol Exp Ther 319(1):1–7CrossRefPubMedGoogle Scholar
  17. Tallarida RJ (2011) Quantitative methods for assessing drug synergism. Gene Cancer 2(11):1003–1008CrossRefGoogle Scholar
  18. Tallarida RJ (2016) Drug combinations: tests and analysis with isoboles. Curr Protoc Pharmacol 72:9.19.1–9.19.19CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Clinical Pharmacology and PharmacometricsBristol-Myers Squibb CompanyPrincetonUSA

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