Development of a method for clinical pharmacokinetic testing to allow for targeted Melphalan dosing in multiple myeloma patients undergoing autologous transplant.
Development of a method for clinical pharmacokinetic testing to allow for targeted Melphalan dosing in multiple myeloma patients undergoing autologous transplant.
复制标题
开发一种临床药代动力学测试方法，以便在接受自体移植的多发性骨髓瘤患者中进行有针对性的美法仑给药。
DOI：
10.1111/bcp.14308
复制
发表时间：
2020
影响因子：
3.4
通讯作者：
Patel,Pritesh
中科院分区：
文献类型：
--
作者：
Sweiss,Karen;Vemu,Bhaskar;Hofmeister,CraigC;Wenzler,Eric;Calip,GregorySampang;Galvin,JohnP;Mahmud,Nadim;Rondelli,Damiano;Johnson,JeremyJames;Patel,Pritesh
高剂量美法兰（HDM）和自体干细胞移植（ASCT）是多发性骨髓瘤（MM）的标准治疗方案，但当使用基于体表面积的剂量时，美法兰暴露量（血浆药物浓度-时间曲线下面积，AUC）存在显著差异。我们的目的是建立一种实时调节美伐兰剂量的药代动力学（PK）测试方法。方法我们在行ASCT的MM患者中进行了美法兰140或200 mg/m2的前瞻性PK研究。20例MM患者在第2天和第1天给予HDM，并在8-10个时间点进行PK采样。所有患者在第2天进行PK检测，5例患者在第1天进行PK检测。结果观察到−2天和−1天AUC的患者间差异小于20%。第2天的AUC范围（4.95-11.28 mg h/L）证实了患者间的显著差异。假设的总剂量范围为133-302 mg/m2，以达到总中位AUC。4个时间点的AUC（0,30,150和240分钟）与8个时间点的AUC高度相关。较高的AUC与发热性中性粒细胞减少的风险增加相关（P = 0.05）。结论：本文概述了在行ASCT的MM患者中使用PK试验来建立新的美法仑剂量的方法，以确定所需的美法仑AUC。
AimsHigh dose melphalan (HDM) and autologous stem cell transplant (ASCT) is standard of care for multiple myeloma (MM), but there is significant variability in melphalan exposure (area under the plasma drug concentration–time curve, AUC) when using body surface area‐based dosing. Our aim was to establish a method of pharmacokinetic (PK) testing for real‐time melphalan dose adjustments.MethodsWe performed a prospective PK study of melphalan 140 or 200 mg/m2in MM patients undergoing ASCT. Twenty MM patients were administered HDM on days −2 and − 1, with PK sampling at 8–10 time points. PK testing was performed on day −2 in all patients, and on day −1 in 5 patients.ResultsLess than 20% interpatient variation in the day −2 and − 1 AUC was observed. The day −2 range in AUC (4.95–11.28 mg h/L) confirmed significant interpatient variability. The hypothetical total dose ranged from 133–302 mg/m2to achieve the total median AUC. A 4‐time point AUC (0, 30, 150 and 240 min) highly correlated with the AUC from the 8‐time point schedule. A higher AUC correlated with increased risk of febrile neutropenia (P =.05).ConclusionHere we outline the methods to establish novel melphalan dosing using PK testing in MM patients undergoing ASCT to target a desired melphalan AUC.