在接受造血干细胞移植的儿童地中海贫血患者中超说明书使用霉酚酸酯的剂量建议:一种基于群体药代动力学研究的方法。

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Lu-Lu Niu, Yong-Jun Liu, Yun Wu, Tian-Min Huang, Ting-Qing Wu, Yang Xiao, Xin Chen, Yi-Lin Luo, Tao-Tao Liu
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引用次数: 0

摘要

背景和目的:作为一种免疫抑制剂,霉酚酸酯(MMF)用于预防造血干细胞移植(HCT)后患者的移植物抗宿主病(GVHD)。本研究旨在建立人群药代动力学模型,模拟HCT地中海贫血(TM)患者的给药方案,以填补MMF给药方案缺失的空白。方法:采用MMF对HCT合并TM患者进行霉酚酸(MPA)血药浓度测定。群体药代动力学(PPK)参数采用NONMEM (Version VII, Level 2.0;ICON开发解决方案,美国马里兰州埃利科特市)项目。蒙特卡罗模拟确定了最佳剂量。结果:共有31例患儿239份血样,MPA的PPK为双室模型。MPA间隙(CL)、中央分布容积(V2)、周围分布容积(V3)、室间间隙(Q)和吸收速率常数(Ka)的典型值分别为14.9 L/h、83.5L、141L、3.13 L/h和1.37/h。CL和V2的个体间变异(iv)分别为35%和41%。模拟结果表明,随着患者体表面积(BSA)值的增加,MMF剂量从500mg开始,每天两次有效。结论:“分层”给药方案包括患者尿素,并按BSA四分位数分层给药,而不是“一剂适用于所有人”的方案,将有助于该人群的MMF治疗个体化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dosage Recommendations for Off-label Use of Mycophenolate Mofetil in Pediatric Patients with Thalassemia Undergoing Hematopoietic Stem Cell Transplantation: An Approach Based on Population Pharmacokinetic Studies.

Background and objectives: As an immunosuppressant, mycophenolate mofetil (MMF) is used to prevent graft versus host disease (GVHD) in patients after hematopoietic stem cell transplantation (HCT). This study aimed to establish a population pharmacokinetic model and simulate the dosage protocol in HCT patients with thalassemia (TM) to fill the gap of lacking MMF dosing regimen.

Methods: The mycophenolic acid (MPA) plasma concentrations were obtained from HCT patients with TM after using MMF. The population pharmacokinetic (PPK) parameters were obtained by NONMEM (Version VII, Level 2.0; ICON Development Solutions, Ellicott City, MD, USA) program. Monte Carlo simulations were used to determine the optimal dosing.

Results: A total of 239 blood samples from 31 pediatric patients were available, the PPK of MPA was described as a two-compartment model. The typical values for MPA clearance (CL), central distribution volume (V2), peripheral distribution volume (V3), intercompartmental clearance (Q), and absorption rate constant (Ka) were 14.9 L/h, 83.5L, 141L, 3.13 L/h, and 1.37/h respectively. The inter-individual variability (IIV) of CL and V2 were 35% and 41%, respectively. Simulation results suggested that, as the patient's body surface area (BSA) value increased, MMF dosage initiated from 500 mg twice daily was effective.

Conclusions: A 'tiered' dosage regimen including patient urea and with doses stratified across BSA quartiles, rather than a 'one dose fits all' regimen, would help individualize MMF therapy in this population.

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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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