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达沙替尼在伴有慢性髓性白血病和慢性肾脏病的血液透析患者中的药代动力学。

Pharmacokinetics of dasatinib in a hemodialysis patient with chronic myeloid leukemia and chronic kidney disease.

机构信息

Department of Hematology, Jyoban Hospital, Tokiwa Foundation, 57 Kaminodai Kamiyunagayamachi Jyoban, Iwaki, Fukushima, 972-8322, Japan.

Department of Internal Medicine, Fukushima Rosai Hospital, Iwaki, Fukushima, Japan.

出版信息

Int J Hematol. 2020 Jul;112(1):115-117. doi: 10.1007/s12185-020-02846-5. Epub 2020 Mar 9.

Abstract

Until now, no studies have addressed the use of dasatinib in hemodialysis patients. Herein, we report the case of a 73-year-old hemodialysis patient with chronic myeloid leukemia (CML) who was treated with dasatinib. For 5 years prior, the patient had received nilotinib for the treatment of CML. Regular hemodialysis was initiated due to progression of hypertensive nephrosclerosis, whereupon nilotinib was discontinued and the patient began receiving 100 mg dose of dasatinib once daily. On dialysis days, dasatinib was administered immediately after completion of dialysis. Four months after starting dasatinib, we performed a pharmacokinetic study. The plasma concentrations of dasatinib before, immediately, and 2 h after the completion of hemodialysis were 7.4, 6.1, and 59.5 ng/mL, respectively. Ultrasound cardiography revealed a gradual decline in ejection fraction during dasatinib therapy. Because the patient's dasatinib trough concentration was higher (6.1 ng/mL) than the target level (1.5 ng/mL), we suspected the development of dasatinib-related heart dysfunction; thus, dasatinib was discontinued 6 months after its initiation. We concluded that hemodialysis patients are potentially vulnerable to the cardiotoxic effects of dasatinib; monitoring of cardiac function and plasma drug concentration may thus be useful in assessing their condition.

摘要

迄今为止,尚无研究探讨达沙替尼在血液透析患者中的应用。在此,我们报告一例 73 岁慢性髓性白血病(CML)患者使用达沙替尼治疗的病例。5 年前,该患者因高血压性肾硬化症进展而开始接受尼洛替尼治疗。由于进展为高血压性肾硬化症,开始进行常规血液透析,遂停用尼洛替尼并开始每日服用 100mg 达沙替尼。在血液透析日,达沙替尼在透析完成后立即给予。开始使用达沙替尼 4 个月后,我们进行了药代动力学研究。血液透析前、透析后立即和 2 小时后达沙替尼的血浆浓度分别为 7.4、6.1 和 59.5ng/mL。超声心动图显示在达沙替尼治疗期间射血分数逐渐下降。由于患者的达沙替尼谷浓度(6.1ng/mL)高于目标水平(1.5ng/mL),我们怀疑发生了达沙替尼相关的心功能障碍;因此,在开始使用达沙替尼 6 个月后停用。我们得出结论,血液透析患者可能容易受到达沙替尼的心脏毒性影响;因此,监测心脏功能和血浆药物浓度可能有助于评估其病情。

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