Petri Camille R, O'Donnell Peter H, Cao Hongyuan, Artz Andrew S, Stock Wendy, Wickrema Amittha, Hard Marjie, van Besien Koen
University of Chicago Pritzker School of Medicine , Chicago, IL , USA.
Leuk Lymphoma. 2014 Dec;55(12):2866-73. doi: 10.3109/10428194.2014.897701. Epub 2014 May 27.
Abstract We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.
摘要 我们在62例参与一项关于氯法拉滨-美法仑-阿仑单抗预处理用于造血干细胞移植（HSCT）的I-II期研究的患者中，研究了氯法拉滨的药代动力学及其与肾毒性的关系。测量了包括氯法拉滨浓度-时间曲线下面积（AUC）、最大浓度和清除率在内的药代动力学参数，并对患者的肾损伤情况进行了监测。所有患者预处理时肌酐值均正常，但超过半数（55%）的患者在给予氯法拉滨后发生了急性肾损伤（AKI）。年龄是AKI最强的预测因素，老年患者风险更高（p = 0.002）。发生AKI的患者氯法拉滨AUC更高，剂量标准化AUC最高的患者发生的AKI分级最严重（p = 0.01）。较低的基线肾功能，即使在正常时，也与氯法拉滨清除率降低相关（p = 0.008）。这些数据表明，即使肾功能表面上正常，对于老年和有风险的患者，也应考虑对氯法拉滨剂量进行肾脏调整。
