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ADME Pharmacogenetics and Its Impact on Drug–Drug Interactions

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Enzyme- and Transporter-Based Drug-Drug Interactions

Abstract

The extent of drug metabolism or drug transport-based pharmacokinetic drug–drug interactions is highly variable between individuals. CYP enzymes such as CYP2B6, CYP2C9, CYP2C19, and CYP2D6 and drug efflux and uptake transporters such as ABCB1 and OAT1B1 display genetic polymorphisms (presence of genetic variants in at least 1% of a population) that may result in altered drug metabolism or transport capacities, respectively. These polymorphisms explain the interindividual variable magnitude of a drug–drug interaction to a significant extent by determining either the substrate susceptibility for interactions or the interaction potential of an inducer or inhibitor. Knowledge of the activity of the enzyme that is responsible for the metabolism of the affected drug or inhibitor can offer vital information when assessing drug interactions. Drug efflux and uptake are increasingly recognized to supplement this information. Nowadays, metabolic and transport statuses are easily accessible by genotyping and are an important prerequisite to fully judge the potential of a drug for drug interactions.

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Authors and Affiliations

  1. Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany

    Reinhold Kerb & Matthias Schwab

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  1. Reinhold Kerb
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  2. Matthias Schwab
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Correspondence to Matthias Schwab .

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  1. Leslie Dan Fac. Pharmacy, University of Toronto, College Street 144, Toronto, M5S 3M2, Canada

    K. Sandy Pang

  2. Bristol-Myers Squibb Company, Princeton, 08543, U.S.A.

    A. David Rodrigues

  3. AstraZeneca UK, Alderley Park, Macclesfield, Cheshire, SK10 4TF, United Kingdom

    Raimund M. Peter

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Kerb, R., Schwab, M. (2010). ADME Pharmacogenetics and Its Impact on Drug–Drug Interactions. In: Pang , K., Rodrigues, A., Peter, R. (eds) Enzyme- and Transporter-Based Drug-Drug Interactions. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0840-7_3

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