Cheng Fang, Cui Zheng, Li Qiang, Wang Liu, Zhang Yu, Li Weiming
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, People's Republic of China.
Drug Des Devel Ther. 2025 May 23;19:4311-4320. doi: 10.2147/DDDT.S521260. eCollection 2025.
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.
Our aim was to explore the application of therapeutic drug monitoring (TDM) as a strategy for optimizing dasatinib dosage in patients with CML-CP.
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) 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 >51.85ng/mL were more likely to achieve MMR, while those with a C 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) >2.48 ng/mL were closely associated with the onset of pleural effusion. Older patients demonstrated higher C and C, irrespective of whether they were on a 50 mg or 100 mg dosage regimen.
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.
尽管已经提出了慢性期慢性髓性白血病（CML-CP）的剂量降低方案，但在为患者个体化确定药物剂量方面仍明显缺乏指导。
我们的目的是探索治疗药物监测（TDM）作为优化CML-CP患者达沙替尼剂量策略的应用。
观察到服用100mg剂量的患者的血药浓度明显高于服用50mg的患者，品牌药和仿制药之间的浓度无明显差异。进一步分析发现峰浓度（C）与临床反应之间存在强相关性（主要分子反应（MMR）：103.8±54.0ng/mL对48.6±13.9ng/mL，P<0.001；深度分子反应（DMR）：112.7±57.6ng/mL对66.2±36.1ng/mL，P=0.001）。C>51.85ng/mL的患者更有可能实现MMR，而C超过112.5ng/mL的患者实现DMR的概率更高。我们成功地根据血药浓度为22例接受一线治疗的患者降低了达沙替尼剂量，且未丧失DMR。此外，谷浓度（C）>2.48ng/mL与胸腔积液的发生密切相关。老年患者无论采用50mg还是100mg剂量方案，其C和C均较高。
基于TDM的剂量优化可为CML-CP患者带来有益的临床结果。此外，在血药浓度方面，我们的研究结果提供了更多证据支持每日50mg的一线治疗方案。
