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Mechanisms of Drug Interactions I: Absorption, Metabolism, and Excretion

  • David M. Burger
  • Lindsey H. M. te Brake
  • Rob E. Aarnoutse
Chapter
Part of the Infectious Disease book series (ID)

Abstract

Understanding the basic mechanisms of drug interactions allows researchers and clinicians to best interpret and apply drug interaction data and make predictions about patient-specific interactions. Drug interactions can occur during the absorption, distribution, metabolism, and excretion phases of drug distribution (pharmacokinetic interactions) and at the site of action (pharmacodynamic interactions). The consequences of unintended interactions can be extremely harmful and potentially fatal, such as those leading to cardiac conduction abnormalities. Knowledge of the mechanisms of drug interactions has also identified useful interactions with therapeutic benefits, such as in the development of feasible dosing regimens for protease inhibitors in the treatment of HIV and hepatitis C infection. This chapter describes the mechanisms of drug interactions for each of the aforementioned pharmacokinetic processes. The cytochrome P450 family of enzymes, the P-glycoprotein drug transporter, and their mechanisms for inhibition, induction, and suppression are reviewed. Preclinical and clinical methods used to study cytochrome P450 are discussed.

Keywords

Pharmacokinetics Pharmacodynamics HIV Hepatitis C CYP450 UGT P-glycoprotein OATP Gastric pH Ritonavir Cobicistat Pharmacogenetics Induction Inhibition Tubular secretion Phenotyping 

Notes

Acknowledgments

We would like to thank Kevin C. Brown and Angela D. M. Kashuba for providing us with the text files of this chapter in the previous edition.

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • David M. Burger
    • 1
  • Lindsey H. M. te Brake
    • 1
  • Rob E. Aarnoutse
    • 1
  1. 1.Department of PharmacyRadboud University Medical CenterNijmegenThe Netherlands

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