梅尔法兰
医学
加药
非金属
药代动力学
人口
粘膜炎
移植
体表面积
分配量
造血干细胞移植
治疗药物监测
肿瘤科
内科学
泌尿科
外科
化疗
环境卫生
作者
Gunjan L. Shah,Jaap Jan Boelens,Dean Carlow,Andrew Lin,Ryan Schofield,Nancy Cruz Sitner,Anna Alperovich,Josel D. Ruiz,Anthony J. Proli,Parastoo B. Dahi,Roni Tamari,Sergio Giralt,Michael Scordo,Rick Admiraal
标识
DOI:10.1007/s40262-021-01093-z
摘要
High-dose melphalan is an integral part of conditioning chemotherapy prior to both autologous and allogeneic hematopoietic cell transplantation. While underexposure may lead to relapse, overexposure may lead to toxicities include mucositis, diarrhea, bone marrow suppression, and rarely sinusoidal obstruction syndrome. In this study, we describe the population pharmacokinetics of high-dose melphalan as a first step towards individualized dosing. Melphalan samples were collected in patients receiving an allogeneic or autologous hematopoietic cell transplantation between August 2016 and August 2020 at the Memorial Sloan Kettering Cancer Center. A population-pharmacokinetic model was developed using NONMEM. Based on a total of 3418 samples from 452 patients receiving a median cumulative dose of 140 mg/m2, a two-compartment population-pharmacokinetic model was developed. Fat-free mass was a covariate for clearance, central volume of distribution, and inter-compartmental clearance, while glomerular filtration rate predicted clearance. Simulation studies showed that based on fixed body surface area-based dosing, renal impairment has a higher impact in increasing melphalan exposure compared with obesity. The proposed model adequately describes the population pharmacokinetics of melphalan in adult patients receiving a hematopoietic cell transplantation. This model can be used to define the therapeutic window of melphalan, and subsequently to develop individualized dosing regimens aiming for that therapeutic window in all patients.
科研通智能强力驱动
Strongly Powered by AbleSci AI