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<p>Chronic myeloid leukemia (CML) treatment with imatinib mesylate often faces challenges due to inter-patient variability in drug response and adverse effects. Genetic polymorphisms in enzymes involved in imatinib metabolism, such as CYP2C8 and CYP3A4, may contribute to this variability. This study aimed to investigate the distribution of CYP2C8*3, CYP2C8*4, and CYP3A4*22 among CML patients and evaluate their impact on imatinib exposure and side effects. A descriptive cross-sectional study was conducted on Palestinian CML patients receiving 400&#xa0;mg daily imatinib between June 2021 and August 2022. Genetic analysis and plasma imatinib levels were determined, along with assessment of demographic and clinical parameters. Results revealed significant associations between CYP2C8*3 genotype and lower imatinib trough concentrations, while CYP2C8*4 and CYP3A4*22 variants showed no significant effects. Imatinib <i>C</i><sub>0</sub> levels correlated with treatment duration but not with age, gender, or weight. Notably, higher <i>C</i><sub>0</sub> levels were linked to specific side effects, including fluid retention, diarrhea, myalgia, and anemia. These findings suggest that pharmacogenetic factors, particularly CYP2C8*3 genotype, may influence imatinib exposure and treatment outcomes in CML patients.</p> Graphical Abstract <p></p>

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Genetic and Non-genetic Correlates of Imatinib Pharmacokinetics and Side Effects of Imatinib in Palestinian Patients with Chronic Myeloid Leukemia

  • 期刊论文

  • 发表日期：

    2025年5月12日

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  • Deema Hilmi Adawi,
  • Ahmad Al-barghouthi,
  • Nadia Ben Fredj,
  • Mustafa Lubada,
  • Dania Osama Njjar,
  • Mahmoud Ruzaygat,
  • Hussein Hallak,
  • Karim Aouam

摘要

Chronic myeloid leukemia (CML) treatment with imatinib mesylate often faces challenges due to inter-patient variability in drug response and adverse effects. Genetic polymorphisms in enzymes involved in imatinib metabolism, such as CYP2C8 and CYP3A4, may contribute to this variability. This study aimed to investigate the distribution of CYP2C8*3, CYP2C8*4, and CYP3A4*22 among CML patients and evaluate their impact on imatinib exposure and side effects. A descriptive cross-sectional study was conducted on Palestinian CML patients receiving 400 mg daily imatinib between June 2021 and August 2022. Genetic analysis and plasma imatinib levels were determined, along with assessment of demographic and clinical parameters. Results revealed significant associations between CYP2C8*3 genotype and lower imatinib trough concentrations, while CYP2C8*4 and CYP3A4*22 variants showed no significant effects. Imatinib C0 levels correlated with treatment duration but not with age, gender, or weight. Notably, higher C0 levels were linked to specific side effects, including fluid retention, diarrhea, myalgia, and anemia. These findings suggest that pharmacogenetic factors, particularly CYP2C8*3 genotype, may influence imatinib exposure and treatment outcomes in CML patients.

Graphical Abstract