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Drug-Drug Interactions Associated with Kinase Inhibitors - Overview of Drug Disposition

Sites of drug disposition

(click to enlarge)

The process of drug disposition and a patient’s exposure to a drug is determined by the absorption, distribution, metabolism, and excretion (ADME) characteristics of the agent.1,2 When any of these parameters are modified, systemic drug exposure might be affected.1 

Drug interactions with kinase inhibitors may occur throughout the ADME process as a result of several factors, including:1-3

  • Drug transporters located in the stomach, intestine, kidney and liver.
  • Modulation of gut absorption in the presence or absence of food or dependent on gastric pH or other factors.
  • Metabolism by cytochrome P450 enzymes located in the intestine, liver and kidney.

References

  1. Mathijssen RH, Sparreboom A, Verweij J. Determining the optimal dose in the development of anti-cancer agents. Nat Rev Clin Oncol 2014; 11: 272-281.
  2. Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer 2006; 6: 546-558.
  3. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 2014; 15: e315-326.

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