Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function.
Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function.
复制标题
甲磺酸艾日布林在肾功能正常和受损的癌症患者中的药代动力学。
DOI：
10.1007/s00280-015-2878-5
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发表时间：
2015
影响因子：
3
通讯作者：
Goel,Sanjay
中科院分区：
文献类型：
--
作者：
Tan,AntoinetteR;Sarantopoulos,John;Lee,Lucy;Reyderman,Larisa;He,Yi;Olivo,Martin;Goel,Sanjay
目的评估肾功能损害对晚期实体瘤成人单剂量甲磺酸艾日布林药代动力学的影响。方法根据肾功能对患者进行分组：中度损害（肌酐清除率 [CrCl] 30–50 mL/min）、重度损害（CrCl 15–29 mL/min）或正常（CrCl ≥80 mL/min）。在每个 21 天的周期中，甲磺酸艾日布林剂量（第 1 天和第 8 天）静脉注射：中度，1.1 mg/m2（周期 1 第 1 天除外，1.4 mg/m2）；严重，0.7 mg/m2；正常，1.4 mg/m2。结果纳入 19 名患者（正常，n = 6；中度，n = 7；重度，n = 6）。肾功能损害与浓度-时间曲线下平均剂量标准化面积增加相关（中度/正常和重度/正常的比率：1.49；90% 置信区间 [CI] 0.9, 2.45）。 CrCl 和肾功能呈正相关，数值斜率较小（0.0184；90% CI -0.00254，0.0394）。中度或重度肾功能不全患者中艾日布林模拟剂量减少 1.1 mg/m2，达到与肾功能正常患者 1.4 mg/m2 相同的暴露量。所有组都有相似的毒性特征，没有意外的不良事件。结论肾损伤降低了艾日布林的清除率并增加了暴露量。药代动力学评估支持中度或重度肾功能不全患者将艾日布林剂量减少至 1.1 mg/m2。ClinicalTrials.gov 标识符 NCT01418677。
PurposeTo evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors.MethodsPatients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30–50 mL/min), severe impairment (CrCl 15–29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m2(except cycle 1 day 1, 1.4 mg/m2); severe, 0.7 mg/m2; normal, 1.4 mg/m2.ResultsNineteen patients were enrolled (normal,n= 6; moderate,n= 7; severe,n= 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration–time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI −0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m2in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m2in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events.ConclusionsRenal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m2in patients with moderate or severe renal impairment.ClinicalTrials.gov IdentifierNCT01418677.