Imatinib pharmacokinetics and creatine kinase levels in chronic myeloid leukemia patients: implications for therapeutic response and monitoring

Abstract

Background: Imatinib treatment for certain cancers can lead to elevated creatine kinase (CK) levels, potentially indicating muscle injury, and ongoing research aims to understand the correlation between imatinib levels and creatine kinase to assess its impact on treatment response.

Methods: This single-center observational study involved 76 chronic myeloid leukemia (CML) patients receiving imatinib treatment, focusing on evaluating drug and metabolite levels using liquid chromatography-mass spectrometry (LC-MS-MS) instrumentation. Serum CK and creatine kinase-MB (CK-MB) levels were assessed using Colorimetric kits.

Results: CK and CK-MB levels were measured, CK showed a median value of 211.5 IU/l and CK-MB showed a median value of 4.4 IU/l. Comparing low and high CK groups, significant differences were found in peak and trough plasma concentrations of imatinib and its metabolites. Correlations between CK levels and pharmacokinetic parameters were explored, with notable associations identified. Binary logistic regression revealed predictors influencing the therapeutic response to imatinib and categorized expected CK levels into high or low, with peak levels of imatinib emerging as a significant predictor for CK level categorization.

Conclusion: The study highlights the link between imatinib's pharmacokinetics and elevated CK levels, indicating a possible correlation between specific metabolites and improved treatment response. Individualized monitoring of CK levels and imatinib pharmacokinetics could enhance care for CML patients.

Keywords: CK levels; CK-MB; Chronic myeloid leukemia; Imatinib; Pharmacokinetics.

Fig. 1

Pharmacokinetics characteristics of study participants categorized by CK levels: A peak imatinib plasma level (ng/ml), B trough imatinib plasma level (ng/ml), C peak N-des-methyl imatinib plasma level (ng/ml), D trough N-des-methyl imatinib plasma level (ng/ml), E peak pyridine-N-oxide imatinib plasma level (ng/ml), F trough pyridine-N-oxide imatinib plasma level (ng/ml), G Ke, H Css (ng/ml), I Vd (L), J Cl (l/h)