Mervat M Omran, Amel B Ibrahim, Raafat Abdelfattah, Samia A Shouman, Marwa S Hamza
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Serum CK and creatine kinase-MB (CK-MB) levels were assessed using Colorimetric kits.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156749/pdf/","citationCount":"0","resultStr":"{\"title\":\"Imatinib pharmacokinetics and creatine kinase levels in chronic myeloid leukemia patients: implications for therapeutic response and monitoring.\",\"authors\":\"Mervat M Omran, Amel B Ibrahim, Raafat Abdelfattah, Samia A Shouman, Marwa S Hamza\",\"doi\":\"10.1007/s00228-024-03675-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>The study highlights the link between imatinib's pharmacokinetics and elevated CK levels, indicating a possible correlation between specific metabolites and improved treatment response. 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引用次数: 0
摘要
背景:伊马替尼治疗某些癌症可导致肌酸激酶(CK)水平升高,这可能预示着肌肉损伤,目前的研究旨在了解伊马替尼水平与肌酸激酶之间的相关性,以评估其对治疗反应的影响:这项单中心观察性研究涉及 76 名接受伊马替尼治疗的慢性髓性白血病(CML)患者,重点是使用液相色谱-质谱联用仪(LC-MS-MS)评估药物和代谢物水平。使用比色试剂盒评估血清肌酸激酶和肌酸激酶-MB(CK-MB)水平:结果:测定的肌酸激酶和肌酸激酶-MB水平,肌酸激酶的中位值为 211.5 IU/l,肌酸激酶-MB 的中位值为 4.4 IU/l。对比低 CK 组和高 CK 组,发现伊马替尼及其代谢物的血浆峰浓度和谷浓度存在显著差异。研究还探讨了肌酸激酶水平与药代动力学参数之间的相关性,并发现了明显的关联。二元逻辑回归揭示了影响伊马替尼治疗反应的预测因素,并将预期的CK水平分为高或低,伊马替尼的峰值水平成为CK水平分类的重要预测因素:结论:这项研究强调了伊马替尼的药代动力学与 CK 水平升高之间的联系,表明特定代谢物与治疗反应改善之间可能存在相关性。对CK水平和伊马替尼药代动力学进行个体化监测可加强对CML患者的治疗。
Imatinib pharmacokinetics and creatine kinase levels in chronic myeloid leukemia patients: implications for therapeutic response and monitoring.
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.
期刊介绍:
The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed.
Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor.
Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves
-a compound that is interesting and new in some basic or fundamental way, or
-methods that are original in some basic sense, or
-a highly unexpected outcome, or
-conclusions that are scientifically novel in some basic or fundamental sense.