title: Therapeutic drug monitoring and tyrosine kinase inhibitors.
abstract: The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under- or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects. Following a literature search on PubMed, studies on TKIs and their pharmacokinetic characteristics, plasma quantification and inter-individual variability was studied. TDM is commonly used in various medical fields, including cardiology and psychiatry, but is not often applied in oncology. Plasma concentration monitoring has been thoroughly studied for imatinib, in order to evaluate the usefulness of TDM. The measurement of plasma concentration can be performed by various analytical techniques, with liquid chromatography-mass spectrometry being the reference method. This method is currently used to monitor the efficacy and tolerability of imatinib treatments. Although TDM is already being used for imatinib, additional studies are required in order to improve this practice with the inclusion of other TKIs.
authors.affiliation: Department of Pharmacology, CHU Clermont-Ferrand, Clermont-Ferrand F-63003, France; INSERM U 1107, Neuro-Dol, Clermont-Ferrand F-63000, France; Centre Jean Perrin, Clermont-Ferrand F-63011, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Herviou
authors.affiliation: Centre Jean Perrin, Clermont-Ferrand F-63011, France; ERTICa EA 4677, Research Team on Individualized Treatment of Cancers in Auvergne, Auvergne University and Centre Jean Perrin, Clermont-Ferrand F-63011, France; INSERM UMR 990, Auvergne University, Clermont-Ferrand F-63000, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Thivat
authors.affiliation: Department of Pharmacology, CHU Clermont-Ferrand, Clermont-Ferrand F-63003, France; INSERM U 1107, Neuro-Dol, Clermont-Ferrand F-63000, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Richard
authors.affiliation: Department of Pharmacology, CHU Clermont-Ferrand, Clermont-Ferrand F-63003, France; INSERM U 1107, Neuro-Dol, Clermont-Ferrand F-63000, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Roche
authors.affiliation: Centre Jean Perrin, Clermont-Ferrand F-63011, France; ERTICa EA 4677, Research Team on Individualized Treatment of Cancers in Auvergne, Auvergne University and Centre Jean Perrin, Clermont-Ferrand F-63011, France; INSERM UMR 990, Auvergne University, Clermont-Ferrand F-63000, France.
authors.forename: Joyce
authors.initials: J
authors.lastname: Dohou
authors.affiliation: Centre Jean Perrin, Clermont-Ferrand F-63011, France; INSERM UMR 990, Auvergne University, Clermont-Ferrand F-63000, France; Clinical Investigation Center, INSERM U 501, Auvergne University, Clermont-Ferrand F-63000, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Pouget
authors.affiliation: Department of Pharmacology, CHU Clermont-Ferrand, Clermont-Ferrand F-63003, France; INSERM U 1107, Neuro-Dol, Clermont-Ferrand F-63000, France; Department of Fundamental and Clinical Pharmacology of Pain, Auvergne University, Clermont-Ferrand F-63000, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.affiliation: Centre Jean Perrin, Clermont-Ferrand F-63011, France; INSERM UMR 990, Auvergne University, Clermont-Ferrand F-63000, France; CREaT EA 3846, Cancer Resistance Exploring and Targeting, Auvergne University and Centre Jean Perrin, Clermont-Ferrand F-63011, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Durando
authors.affiliation: Department of Pharmacology, CHU Clermont-Ferrand, Clermont-Ferrand F-63003, France; INSERM U 1107, Neuro-Dol, Clermont-Ferrand F-63000, France; Department of Fundamental and Clinical Pharmacology of Pain, Auvergne University, Clermont-Ferrand F-63000, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Authier
keywords: pharmacokinetics; plasma concentration; target value; therapeutic drug monitoring; tyrosine kinase inhibitor