Population Pharmacokinetic Model of Intravenous Immunoglobulin in Patients Treated for Various Immune System Disorders.

IF 3.2 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Clinical therapeutics Pub Date : 2024-12-01 Epub Date: 2024-10-04 DOI:10.1016/j.clinthera.2024.09.018
Jian Lynn Lee, Noraida Mohamed Shah, Mohd Makmor-Bakry, Farida Islahudin, Hamidah Alias, Shamin Mohd Saffian
{"title":"Population Pharmacokinetic Model of Intravenous Immunoglobulin in Patients Treated for Various Immune System Disorders.","authors":"Jian Lynn Lee, Noraida Mohamed Shah, Mohd Makmor-Bakry, Farida Islahudin, Hamidah Alias, Shamin Mohd Saffian","doi":"10.1016/j.clinthera.2024.09.018","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Intravenous immunoglobulin (IVIG) is used to treat various immune system disorders, but the factors influencing its disposition are not well understood. This study aimed to estimate the population pharmacokinetic parameters of IVIG and to investigate the effect of genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor (FcRn) and clinical variability on the pharmacokinetic properties of IVIG in patients with immune system disorders.</p><p><strong>Methods: </strong>Patients were recruited from 4 hospitals in Malaysia. Clinical data were recorded, and blood samples were taken for pharmacokinetic and genetic studies. Population pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling in Monolix. Age, weight, baseline immunoglobulin G concentration, ethnicity, sex, genotype, disease type, and comorbidity were investigated as potential covariates. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive checks, and bootstrap analysis.</p><p><strong>Findings: </strong>A total of 292 blood samples were analyzed from 79 patients. The IVIG concentrations were best described by a 2-compartment model with linear elimination. Weight was found to be an important covariate for volume of distribution in the central compartment (Vc), volume of distribution in the peripheral compartment (Vp), and clearance in the central compartment, whereas disease type was found to be an important covariate for Vp. Goodness-of-fit plots indicated that the model fit the data adequately. Genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor did not affect the pharmacokinetic properties of IVIG.</p><p><strong>Implications: </strong>This study supports the use of dosage based on weight as per current practice. The study findings highlight that Vp is significantly influenced by the type of disease being treated with IVIG. This relationship suggests that different disease types, particularly inflammatory and autoimmune conditions, may alter tissue permeability and fluid distribution due to varying degrees of inflammation. Increased inflammation can lead to enhanced permeability and retention of IVIG in peripheral tissues, reflecting higher Vp values.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":"e25-e37"},"PeriodicalIF":3.2000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.clinthera.2024.09.018","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/4 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: Intravenous immunoglobulin (IVIG) is used to treat various immune system disorders, but the factors influencing its disposition are not well understood. This study aimed to estimate the population pharmacokinetic parameters of IVIG and to investigate the effect of genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor (FcRn) and clinical variability on the pharmacokinetic properties of IVIG in patients with immune system disorders.

Methods: Patients were recruited from 4 hospitals in Malaysia. Clinical data were recorded, and blood samples were taken for pharmacokinetic and genetic studies. Population pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling in Monolix. Age, weight, baseline immunoglobulin G concentration, ethnicity, sex, genotype, disease type, and comorbidity were investigated as potential covariates. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive checks, and bootstrap analysis.

Findings: A total of 292 blood samples were analyzed from 79 patients. The IVIG concentrations were best described by a 2-compartment model with linear elimination. Weight was found to be an important covariate for volume of distribution in the central compartment (Vc), volume of distribution in the peripheral compartment (Vp), and clearance in the central compartment, whereas disease type was found to be an important covariate for Vp. Goodness-of-fit plots indicated that the model fit the data adequately. Genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor did not affect the pharmacokinetic properties of IVIG.

Implications: This study supports the use of dosage based on weight as per current practice. The study findings highlight that Vp is significantly influenced by the type of disease being treated with IVIG. This relationship suggests that different disease types, particularly inflammatory and autoimmune conditions, may alter tissue permeability and fluid distribution due to varying degrees of inflammation. Increased inflammation can lead to enhanced permeability and retention of IVIG in peripheral tissues, reflecting higher Vp values.

各种免疫系统疾病患者静脉注射免疫球蛋白的群体药代动力学模型。
目的:静脉注射免疫球蛋白(IVIG)用于治疗各种免疫系统疾病,但影响其处置的因素尚不十分清楚。本研究旨在估算 IVIG 的群体药代动力学参数,并调查编码新生儿 Fc 受体(FcRn)的 FCGRT 基因的遗传多态性和临床变异性对免疫系统疾病患者 IVIG 药代动力学特性的影响:方法:从马来西亚的 4 家医院招募患者。方法:从马来西亚的 4 家医院招募患者,记录临床数据,并抽取血液样本进行药代动力学和遗传学研究。通过 Monolix 中的非线性混合效应模型估算人群药代动力学参数。年龄、体重、基线免疫球蛋白 G 浓度、种族、性别、基因型、疾病类型和合并症作为潜在的协变量进行了研究。使用目标函数值差异、拟合优度图、视觉预测检查和引导分析对模型进行了评估:共分析了 79 名患者的 292 份血液样本。用线性消除的 2 室模型对 IVIG 浓度进行了最佳描述。体重是中心室分布容积(Vc)、外周室分布容积(Vp)和中心室清除率的重要协变量,而疾病类型是 Vp 的重要协变量。拟合优度图表明该模型充分拟合了数据。编码新生儿 Fc 受体的 FCGRT 基因的遗传多态性不会影响 IVIG 的药代动力学特性:本研究支持按照目前的做法使用基于体重的剂量。研究结果表明,Vp 受 IVIG 治疗的疾病类型的显著影响。这种关系表明,不同类型的疾病,尤其是炎症和自身免疫性疾病,可能会因不同程度的炎症而改变组织的通透性和液体分布。炎症加重会导致 IVIG 在外周组织中的渗透性和滞留性增强,从而反映出更高的 Vp 值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Clinical therapeutics
Clinical therapeutics 医学-药学
CiteScore
6.00
自引率
3.10%
发文量
154
审稿时长
9 weeks
期刊介绍: Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信