Adawi Deema Hilmi, Al-Barghouthi Ahmad, Fredj Nadia Ben, Lubada Mustafa, Njjar Dania Osama, Ruzaygat Mahmoud, Hallak Hussein, Aouam Karim
Department of Pharmacology, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Department of Pharmacology, Palestinian Ministry of Health, Ramallah, Palestine.
Biochem Genet. 2025 May 12. doi: 10.1007/s10528-025-11130-2.
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 CYP2C83, CYP2C84, and CYP3A422 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 CYP2C83 genotype and lower imatinib trough concentrations, while CYP2C84 and CYP3A422 variants showed no significant effects. Imatinib C levels correlated with treatment duration but not with age, gender, or weight. Notably, higher C 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.
由于患者间药物反应和不良反应存在差异，甲磺酸伊马替尼治疗慢性髓性白血病（CML）常面临挑战。参与伊马替尼代谢的酶的基因多态性，如CYP2C8和CYP3A4，可能导致这种差异。本研究旨在调查CML患者中CYP2C83、CYP2C84和CYP3A422的分布情况，并评估它们对伊马替尼暴露量和副作用的影响。对2021年6月至2022年8月期间每天接受400mg伊马替尼治疗的巴勒斯坦CML患者进行了一项描述性横断面研究。测定了基因分析、血浆伊马替尼水平，并评估了人口统计学和临床参数。结果显示，CYP2C83基因型与较低的伊马替尼谷浓度之间存在显著关联，而CYP2C84和CYP3A422变异体未显示出显著影响。伊马替尼C水平与治疗持续时间相关，但与年龄、性别或体重无关。值得注意的是，较高的C水平与特定的副作用有关，包括液体潴留、腹泻、肌痛和贫血。这些发现表明，药物遗传学因素，特别是CYP2C8*3基因型，可能影响CML患者的伊马替尼暴露量和治疗结果。
