• Masatomo Miura and Naoto Takahashi.
• Department of Pharmacy, Akita University Hospital.
• Rinsho Ketsueki. 2019 Jan 1; 60 (9): 1140-1147.

AbstractImatinib, nilotinib, dasatinib, bosutinib, and ponatinib are tyrosine kinase inhibitors used to treat chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and target concentration intervention (TCI) are novel strategies that use concentration-controlled dosing (CCD) to attain a faster and more profound clinical response in patients with CML. The target plasma trough concentration (C0) of imatinib is 1,000 ng/ml to obtain a higher major molecular response (MMR) rate. Target nilotinib and bosutinib C0 of 900 and 62 ng/ml, respectively, are recommended to attain a better response, whereas a target ponatinib C0 of 21.3 ng/ml has been proposed to obtain a better response and decrease the risk of adverse events, such as vascular toxicity. Approaches for these four TKIs involve the use of TCI with specific target concentrations rather than TDM with a therapeutic range. Conversely, for dasatinib, a lower C0 of <4.33 ng/ml is the maximum toxic concentration recommended to avoid pleural effusion. Therefore, precision dosing using CCD of TKIs for CML could maximize the clinical benefit and minimize toxicity.

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