Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients

Tyrosine kinase inhibitors work by blocking the tyrosine kinases responsible for the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patients, and most of them were paediatrics. A total of 82.4% of the patients were men; however, sex-related differences in the drugs' pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that therapeutic drug monitoring is a useful method for adjusting a patient's treatment schedule that depends on drug concentrations in biological fluids. The use of therapeutic drug monitoring in conjunction with tyrosine kinase inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, the tyrosine kinase inhibitor therapeutic drug monitoring classification needs to be refined in terms of factors like sex and age.

Automated summary

This study examined the influence of age and sex on the levels of tyrosine kinase inhibitors in plasma and cerebrospinal fluid of patients with chronic myeloid leukaemia. Results showed an inverse correlation between age and imatinib plasma concentration, and lower dasatinib concentrations in plasma compared to cerebrospinal fluid, especially in paediatric patients. Therapeutic drug monitoring, along with tyrosine kinase inhibitors, is supported for the treatment of chronic myeloid leukaemia. Refinement of the classification of tyrosine kinase inhibitor therapeutic drug monitoring should consider factors like sex and age.