Kronik Miyeloid Lösemi Hastalarında İmatinib ve Norimatinib Plazma Düzeyi Ölçümleri

Abstract

Objective: Imatinib is the first line treatment in chronic myeloid leukemia (CML). Imatinib metabolism depends primarily on the presence of cytochrome P450 enzymes, its active metabolite being norimatinib (N-desmethyl imatinib). Norimatinib accumulates in plasma 10-30%. The aim of this study was to analyze certain parameters which maintain the importance in clarifying the pharmacologic effects of imatinib. Material and Methods: To investigate plasma concentrations, 41 CML patients on minimum 400 mg imatinib daily were included to the study. Pharmacokinetic analysis was performed by tandem mass spectrometry (LC-MS/MS). Mean plasma imatinib and norimatinib levels were statistically calculated as 4.038±1.290 ppm (min. 0.576 ppm, max. 6.795 ppm) and 1.150±0.733 ppm (min. 0.08 ppm, max. 3.835 ppm), respectively. Results: Limit of detection (LOD) values for imatinib and norimatinib were 30 ppb and 25 ppb, whereas limit of quantification (LOQ) values were 99 ppb and 82.5 ppb, and recovery of imatinib and norimatinib were 98.45% and 92.47%, respectively. Average percentage of imatinib transformation to norimatinib was 22.16%. Variation of this percentage from one patient to another suggested the possibility of interindividual differences in drug response. Conclusion: Individual results have shown that pharmacologic effects of imatinib may differentiate among patients. In this study, we standardized and justified the applicability of our analysis method. Patients' plasma drug levels can be measured using this method. Thus optimal treatment efficacy can be ensured.