Therapeutic Drug Monitoring of Imatinib: Is There a Rationale for Also Quantifying Its Active Metabolite?

IF 2 4区医学 Q3 ONCOLOGY

Chemotherapy Pub Date : 2024-10-11 DOI:10.1159/000541936

Clara Eschalier, Thierry Lafont, Sabrina Marsili, Malika Yakoubi, Aurélie Brice, Fabienne Thomas, Mélanie White-Koning, Ben Allal, Etienne Chatelut

{"title":"Therapeutic Drug Monitoring of Imatinib: Is There a Rationale for Also Quantifying Its Active Metabolite?","authors":"Clara Eschalier, Thierry Lafont, Sabrina Marsili, Malika Yakoubi, Aurélie Brice, Fabienne Thomas, Mélanie White-Koning, Ben Allal, Etienne Chatelut","doi":"10.1159/000541936","DOIUrl":null,"url":null,"abstract":"Introduction: Therapeutic drug monitoring of imatinib is widely performed to individualize imatinib dosage. While N-desmethyl imatinib is an active metabolite of imatinib, its concentrations are not routinely determined.Methods: Imatinib and N-desmethyl imatinib trough plasma concentrations at steady-state were obtained from 295 patients with either chronic myeloid leukemia or gastrointestinal stromal tumor to see whether N-desmethyl imatinib provided additional information. Pharmacokinetic data were analyzed using a nonlinear mixed effect approach. Correlations between several pharmacokinetic metrics of drug exposure were evaluated.Results: The mean value of the N-desmethyl imatinib/imatinib ratio of trough concentrations was 0.31 with half of the values between 0.23 and 0.37. N-desmethyl imatinib and total (i.e., N-desmethyl imatinib plus imatinib) trough plasma concentrations or area under the curve values were closely correlated with imatinib values. The distribution of imatinib or total concentrations between patients requiring imatinib dosage adjustment, or not, was similar.Conclusion: These results do not clearly support routine N-desmethyl monitoring since it does not provide additional information to imatinib data.","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-11"},"PeriodicalIF":2.0000,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000541936","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Therapeutic drug monitoring of imatinib is widely performed to individualize imatinib dosage. While N-desmethyl imatinib is an active metabolite of imatinib, its concentrations are not routinely determined.

Methods: Imatinib and N-desmethyl imatinib trough plasma concentrations at steady-state were obtained from 295 patients with either chronic myeloid leukemia or gastrointestinal stromal tumor to see whether N-desmethyl imatinib provided additional information. Pharmacokinetic data were analyzed using a nonlinear mixed effect approach. Correlations between several pharmacokinetic metrics of drug exposure were evaluated.

Results: The mean value of the N-desmethyl imatinib/imatinib ratio of trough concentrations was 0.31 with half of the values between 0.23 and 0.37. N-desmethyl imatinib and total (i.e., N-desmethyl imatinib plus imatinib) trough plasma concentrations or area under the curve values were closely correlated with imatinib values. The distribution of imatinib or total concentrations between patients requiring imatinib dosage adjustment, or not, was similar.

Conclusion: These results do not clearly support routine N-desmethyl monitoring since it does not provide additional information to imatinib data.

查看原文本刊更多论文

伊马替尼的治疗药物监测：同时量化其活性代谢物是否合理？

导言：伊马替尼的治疗药物监测被广泛应用于伊马替尼剂量的个体化。虽然N-去甲基伊马替尼是伊马替尼的一种活性代谢产物，但其浓度并未常规测定：方法：从295名慢性髓性白血病或胃肠道间质瘤患者中获得了伊马替尼和N-去甲基伊马替尼稳态时的血浆谷浓度，以了解N-去甲基伊马替尼是否能提供更多信息。药代动力学数据采用非线性混合效应方法进行分析。评估了药物暴露的几个药代动力学指标之间的相关性：结果：N-去甲基伊马替尼/伊马替尼谷浓度比值的平均值为0.31，其中一半的比值介于0.23-0.37之间。N-去甲基伊马替尼和总（即N-去甲基伊马替尼加伊马替尼）血浆谷浓度或曲线下面积值与伊马替尼值密切相关。需要或不需要调整伊马替尼剂量的患者的伊马替尼或总浓度分布情况相似：这些结果并不明确支持常规的N-去甲基监测，因为它并不能为伊马替尼数据提供额外的信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Chemotherapy 医学-药学

CiteScore

5.80

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal publishes original research articles and state-of-the-art reviews on all aspects of antimicrobial and antitumor chemotherapy. The results of experimental and clinical investigations into the microbiological and pharmacologic properties of antibacterial, antiviral and antitumor compounds are major topics of publication. Papers selected for the journal offer data concerning the efficacy, toxicology, and interactions of new drugs in single or combined applications. Studies designed to determine the pharmacokinetic and pharmacodynamics properties of similar preparations and comparing their efficacy are also included. Special emphasis is given to the development of drug-resistance, an increasing problem worldwide.