Dasatinib Dose Optimization Based on Therapeutic Drug Monitoring in Patients with Chronic-Phase Chronic Myeloid Leukemia.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-05-23 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S521260

Fang Cheng, Zheng Cui, Qiang Li, Liu Wang, Yu Zhang, Weiming Li

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引用次数: 0

Abstract

Background: Although a dosage decrease regimen for chronic phase chronic myeloid leukemia (CML-CP) has been suggested, there is a marked lack of guidance on individualizing medication dosages for patients.

Methods: Our aim was to explore the application of therapeutic drug monitoring (TDM) as a strategy for optimizing dasatinib dosage in patients with CML-CP.

Results: It was observed that patients administered a dosage of 100 mg exhibited significantly higher concentrations than those given 50 mg, with no marked difference in concentration between branded and generic drugs. Further analysis unveiled a robust correlation between peak concentration (C_max) and clinical response (major molecular response (MMR): 103.8 ± 54.0 ng/mL versus 48.6 ± 13.9 ng/mL, P < 0.001; deep molecular response (DMR): 112.7 ± 57.6 ng/mL versus 66.2 ± 36.1 ng/mL, P = 0.001). Patients with a C_max >51.85ng/mL were more likely to achieve MMR, while those with a C_max surpassing 112.5 ng/mL had a higher probability of attaining DMR. We successfully implemented dasatinib dose reduction based on concentrations without loss of DMR in 22 patients undergoing first-line therapy. Moreover, trough concentrations (C_min) >2.48 ng/mL were closely associated with the onset of pleural effusion. Older patients demonstrated higher C_min and C_max, irrespective of whether they were on a 50 mg or 100 mg dosage regimen.

Conclusion: TDM-based dose optimization could lead to beneficial clinical outcomes for patients with CML-CP. Furthermore, in terms of blood drug concentration, our findings supply additional evidence supporting the first-line treatment regimen of 50 mg daily.

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基于治疗药物监测的达沙替尼在慢性粒细胞白血病患者中的剂量优化。

背景：虽然已经提出了慢性粒细胞白血病（CML-CP）的减量方案，但明显缺乏对患者个体化用药剂量的指导。方法：我们的目的是探讨治疗药物监测（TDM）作为优化CML-CP患者达沙替尼剂量的策略。结果：观察到100mg剂量的患者浓度明显高于50mg剂量的患者，而品牌药和仿制药的浓度无显著差异。进一步分析显示，峰值浓度（Cmax）与临床反应(主要分子反应（MMR）之间存在显著相关性：103.8±54.0 ng/mL vs 48.6±13.9 ng/mL, P < 0.001；深度分子反应（DMR）： 112.7±57.6 ng/mL vs 66.2±36.1 ng/mL, P = 0.001)。Cmax值为51.85ng/mL的患者更有可能实现MMR，而Cmax值超过112.5 ng/mL的患者更有可能实现DMR。我们在22名接受一线治疗的患者中成功实施了基于浓度的达沙替尼剂量减少，没有DMR损失。此外，谷浓度（Cmin） bb0 2.48 ng/mL与胸腔积液的发生密切相关。老年患者表现出较高的Cmin和Cmax，无论他们是服用50mg还是100mg的剂量方案。结论：基于tdm的剂量优化可为CML-CP患者带来良好的临床结果。此外，就血药浓度而言，我们的研究结果提供了额外的证据，支持每天50毫克的一线治疗方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.