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患者特异性药理动力学和达沙替尼的毒性
Benjamin O Adegbite1,2, Matthew H Abramson1, Victoria Gutgarts3
1Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
概括
与其他氨酸激酶抑制剂相比,达沙替尼使用显著增加了患蛋白尿症 (一种损伤形式) 的风险. 高达沙提尼布血度与蛋白尿风险增加相关.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 达沙替尼是一种氨酸激酶抑制剂,与潜在的毒性有关.
- 在接受氨酸激酶抑制剂治疗的患者中,淋巴细胞损伤是令人担忧的.
研究的目的:
- 为了研究用达沙替尼布治疗的患者中蛋白尿的发生率.
- 为了确定与达沙替尼布诱导的球损伤相关的风险因素.
主要方法:
- 在82名慢性骨髓性白血病患者中,使用尿中的白血素-肌素比率 (UACR) 评估了质损伤,这些患者至少90天服用了类铁酶抑制剂.
- 在达沙替尼使用者和使用其他氨酸激酶抑制剂者之间比较UACR水平.
- 分析了达沙替尼的血药理动力学和与蛋白尿症发展相关的药物度.
- 包括一个病例研究,一个患有脏范围蛋白尿症的患者接受了达沙替尼.
主要成果:
- 与其他铁激酶抑制剂使用者 (n=50,中位数15.0 mg/g;P<0.001) 相比,达沙替尼使用者 (n=32) 的UACR水平显著更高 (中位数28.0 mg/g).
- 10%的达沙替尼布使用者表现出严重增加的白色素尿 (UACR>300 mg/g),而另一组没有.
- 与UACR (ρ=0.54,P=0.03) 和治疗持续时间 (P=0.003) 正相关的达沙替尼的平均血度.
- 在案例研究中,脏活检显示了淋巴细胞损伤,该损伤在停止使用达沙提尼布后消失.
结论:
- 与其他氨酸激酶抑制剂相比,达沙替尼暴露与蛋白尿症的发生率显著增加有关.
- 达沙提尼布血度升高是治疗期间蛋白尿症发生的关键危险因素.
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