Pharmacocinétique des inhibiteurs de tyrosine kinase dans la leucémie myéloïde chronique

Tyrosine-kinase inhibitors and their first representant, imatinib, are a new pharmacologic family currently used in oncology. Imatinib is active by orale route, and became a gold standard in the treatment of chronic myelogenous leukaemia and gastro-intestinal stromal tumors. Knowledge of pharmacokinetic leads to understand mechanism of activity, and reasons for some clinical failures. Pharmacokinetics of imatinib is characterized by a large inter-patient variability due to drug-drug interactions and genetic polymorphism, in cytochromes P450 and transport proteins as Pgp. Mutation in biological target is a main cause of resistance but pharmacokinetic variability may also lead to sub-inhibitory plasmatic concentrations of imatinib. Correlation between plasmatic concentration of imatinib and clinical response is now well established. New tyrosine-kinase inhibitors as dasatinib and nilotinib became promising alternative drugs. Knowledge of their pharmacokinetic could lead also to a better use.