Abstract
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.
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References
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, 2011
Allard B, Aspeslagh S, Garaud S et al (2018) Immuno-oncology-101: overview of major concepts and translational perspectives. Semin Cancer Biol. https://doi.org/10.1016/j.semcancer.2018.02.005
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58
Chou (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58:621–681
CURRENT–OASIS 7 Investigators (2010) Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 363:930–942
EMA (2012) Guideline on the investigation of drug interactions
FDA (2017) Guidance for industry, in vitro metabolism- and transporter-mediated drug-drug interaction studies
Gadkar K, Kirouac D, Parrott N et al (2016) Quantitative systems pharmacology: a promising approach for translational pharmacology. Drug Discov Today Technol 21–22:57–65
Gibaldi M, Perrier D (1982) Kinetics of pharmacologic response. In: pharmacokinetics, 2nd edn. Marcel Dekker, New York, p 222
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):247–262
Leil TA, Ermakov S (2015) Editorial: the emerging discipline of quantitative systems pharmacology. Front Pharmacol 30(6):129
Montgomery AA, Peters TJ, Little P (2003) Design, analysis and presentation of factorial randomized controlled trials. BMC Med Res Methodol 24(3):26
Pandis N, Walsh T, Polychronopoulou A et al (2014) Factorial designs: an overview with applications to orthodontic clinical trials. Eur J Orthod 36(3):314–320
Pocock SJ, Clayton TC, Stone GW (2015) Challenging issues in clinical trial design. J Am Coll Cardiol 66(25):2886–2898
Schild HO (1957) Drug antagonism and pA2. Pharmacol Rev 9:242–246
Tallarida RJ (2006) An overview of drug combination analysis with isobolograms. J Pharmacol Exp Ther 319(1):1–7
Tallarida RJ (2011) Quantitative methods for assessing drug synergism. Gene Cancer 2(11):1003–1008
Tallarida RJ (2016) Drug combinations: tests and analysis with isoboles. Curr Protoc Pharmacol 72:9.19.1–9.19.19
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Zheng, M. (2018). Pharmacodynamic Drug–Drug Interactions. In: Hock, F., Gralinski, M. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-56637-5_29-1
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DOI: https://doi.org/10.1007/978-3-319-56637-5_29-1
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