Analysis of Concentrations of Monomethyl Fumarate in Patients with Multiple Sclerosis: Result from Routine Health Care

Zuzana Krska Kusnirikova, Ivana Kacirova, Veronika Pesakova, Pavel Hradilek, Hana Brozmanova, Milan Grundmann
{"title":"Analysis of Concentrations of Monomethyl Fumarate in Patients with Multiple Sclerosis: Result from Routine Health Care","authors":"Zuzana Krska Kusnirikova, Ivana Kacirova, Veronika Pesakova, Pavel Hradilek, Hana Brozmanova, Milan Grundmann","doi":"10.2174/0118715273302279240529104919","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Dimethyl fumarate is used to treat patients with relapsing-remitting multiple sclerosis. After ingestion, it is rapidly hydrolyzed to the active primary metabolite monomethyl fumarate.</p><p><strong>Objective: </strong>The main objective of our study was to analyze serum concentrations of monomethyl fumarate during routine health care in patients with multiple sclerosis treated with a fixed dose of dimethyl fumarate.</p><p><strong>Methods: </strong>In the pilot cross-sectional study, data from 42 patients treated with dimethyl fumarate at a dose of 240 mg twice daily were collected. Concentrations of the active metabolite monomethyl fumarate were determined at 1-8 h (median, 3 h) or 10-14 h (median, 13 h) after taking the dose. The relationship between monomethyl fumarate concentrations and absolute lymphocyte count was evaluated.</p><p><strong>Results: </strong>Concentrations of monomethyl fumarate ranged from 2.5-3177.9 μg/L, with most concentrations being undetectable approximately 10 hours after administration. In the 1-8 h (median, 3 h) post-dose subgroup, the concentration/dose ratio ranged widely from 0.04-6.62. The median concentration of monomethyl fumarate in the group with the absolute lymphocyte count <0.8 x 10^9/l was more than four times higher than in the group with the absolute lymphocyte count ≥0.8 x 10^9/l (median 440.1 μg/L versus 98.4 μg/L).</p><p><strong>Conclusion: </strong>The wide interindividual variability in monomethyl fumarate pharmacokinetics could contribute to the differential response to dimethyl fumarate in multiple sclerosis patients. A nonsignificant but noticeable trend was observed in the relationship of higher serum monomethyl fumarate concentrations to absolute lymphocyte counts.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":"1516 - 1523"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS & neurological disorders drug targets","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118715273302279240529104919","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Dimethyl fumarate is used to treat patients with relapsing-remitting multiple sclerosis. After ingestion, it is rapidly hydrolyzed to the active primary metabolite monomethyl fumarate.

Objective: The main objective of our study was to analyze serum concentrations of monomethyl fumarate during routine health care in patients with multiple sclerosis treated with a fixed dose of dimethyl fumarate.

Methods: In the pilot cross-sectional study, data from 42 patients treated with dimethyl fumarate at a dose of 240 mg twice daily were collected. Concentrations of the active metabolite monomethyl fumarate were determined at 1-8 h (median, 3 h) or 10-14 h (median, 13 h) after taking the dose. The relationship between monomethyl fumarate concentrations and absolute lymphocyte count was evaluated.

Results: Concentrations of monomethyl fumarate ranged from 2.5-3177.9 μg/L, with most concentrations being undetectable approximately 10 hours after administration. In the 1-8 h (median, 3 h) post-dose subgroup, the concentration/dose ratio ranged widely from 0.04-6.62. The median concentration of monomethyl fumarate in the group with the absolute lymphocyte count <0.8 x 10^9/l was more than four times higher than in the group with the absolute lymphocyte count ≥0.8 x 10^9/l (median 440.1 μg/L versus 98.4 μg/L).

Conclusion: The wide interindividual variability in monomethyl fumarate pharmacokinetics could contribute to the differential response to dimethyl fumarate in multiple sclerosis patients. A nonsignificant but noticeable trend was observed in the relationship of higher serum monomethyl fumarate concentrations to absolute lymphocyte counts.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
多发性硬化症患者富马酸单甲酯浓度分析:常规医疗保健的结果。
背景:富马酸二甲酯用于治疗复发-缓解型多发性硬化症患者。富马酸二甲酯摄入后会迅速水解为活性初级代谢物富马酸单甲酯:我们研究的主要目的是分析接受固定剂量富马酸二甲酯治疗的多发性硬化症患者在日常保健过程中血清中富马酸单甲酯的浓度:在这项试验性横断面研究中,收集了42名接受富马酸二甲酯治疗的患者的数据,治疗剂量为240毫克,每天两次。在服药后 1-8 小时(中位数为 3 小时)或 10-14 小时(中位数为 13 小时)测定活性代谢物富马酸单甲酯的浓度。评估了富马酸单甲酯浓度与淋巴细胞绝对计数之间的关系:结果:富马酸单甲酯的浓度范围为 2.5-3177.9 μg/L,大多数浓度在服药后 10 小时左右检测不到。在给药后 1-8 小时(中位数为 3 小时)的亚组中,浓度/剂量比范围很广,从 0.04-6.62 不等。在淋巴细胞绝对计数组中,富马酸单甲酯的中位浓度为 0.04-6.62:富马酸单甲酯药代动力学的个体间差异很大,这可能是多发性硬化症患者对富马酸二甲酯反应不同的原因之一。在较高的血清富马酸单甲酯浓度与绝对淋巴细胞计数的关系中,观察到了一种不显著但明显的趋势。
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 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors. Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-Loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways. Parkinson's Disease: A Progressive Neurodegenerative Disorder and Structure-Activity Relationship of MAO Inhibitor Scaffolds as an Important Therapeutic Regimen. Exploring Therapeutic Strategies: The Relationship between Metabolic Disorders and FOXO Signalling in Alzheimer's Disease. Proposed Hypothesis of TWEAK/Fn14 Receptor Modulation in Autism Spectrum Disorder.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1