John Libbey Eurotext

Hépato-Gastro & Oncologie Digestive

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Tyrosine Kinase Inhibitors: Interest of the pharmacology and main errors to avoid Volume 26, issue 2, Février 2019

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Authors
1 Institut Gustave Roussy, Service d’oncologie médicale, Gustave Roussy, 114 rue Édouard-Vaillant, 94805 Villejuif Cedex
2 Hôpital Cochin, Service de gastroentérologie et d’oncologie digestive, 27 rue du Faubourg St Jacques, 75014 Paris
* Correspondance

Recent years have been associated with the development of tyrosine kinase inhibitors (TKIs) in digestive oncology. TKIs inhibit the phosphorylation of tyrosine kinases or serine/threonine kinases in the cell membrane. With TKIs, it is not uncommon to observe a dose reduction or even a discontinuation of treatment. All this calls for the development of a personalized dosage in order to optimize treatment. The very high incidence of adverse events suggests that TKIs have a narrow therapeutic window. ITKs have a low bioavailability, lower than 30%, which explains the large variation between individuals. Current validated pharmacological models exist for imatinib, sorafenib and sunitinib to allow a routine pharmacological patient monitoring.Several factors have been identified as modifying the drug concentration or the area under a curve (AUC) of some ITKs, including intake splitting, gastrectomy, bariatric surgery, proton pump inhibitors and are to be considered when prescribing TKIs. Also, some potential errors regarding prescription modalities were identified (time of intake, distance from meals, risk of non-observance, and intake of inducing products).

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