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.
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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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Burger, D.M., te Brake, L.H.M., Aarnoutse, R.E. (2018). Mechanisms of Drug Interactions I: Absorption, Metabolism, and Excretion. In: Pai, M., Kiser, J., Gubbins, P., Rodvold, K. (eds) Drug Interactions in Infectious Diseases: Mechanisms and Models of Drug Interactions. Infectious Disease. Humana Press, Cham. https://doi.org/10.1007/978-3-319-72422-5_2
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