基于生理的药代动力学模型预测妊娠期间托吡酯的母体药代动力学变化并推荐剂量调整。

IF 2.3 4区 医学
Yuying Chen, Meng Ke, Wanhong Wu, Cuihong Lin
{"title":"基于生理的药代动力学模型预测妊娠期间托吡酯的母体药代动力学变化并推荐剂量调整。","authors":"Yuying Chen, Meng Ke, Wanhong Wu, Cuihong Lin","doi":"10.1002/jcph.70105","DOIUrl":null,"url":null,"abstract":"<p><p>Topiramate is increasingly used in the treatment of epilepsy during pregnancy. However, its plasma concentration evidently decreases during pregnancy, which may reduce its efficacy. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of topiramate to simulate maternal and fetal pharmacokinetic changes across different trimesters and to propose dose adjustments. We established a topiramate pregnancy PBPK model in PK-Sim and Mobi. The model was validated using clinically observed data and subsequently used to optimize the dosage during pregnancy. Simulation results showed that the mean steady-state trough plasma concentration of topiramate decreased by 9.4%, 32%, and 46% in the first, second, and third trimesters, respectively. Based on these findings, the dosage should remain unchanged during the first trimester of pregnancy. However, increasing the baseline dose of topiramate by at least 1.5- and 1.9-fold during the second and third trimesters, respectively, may help maintain effective plasma concentrations. This study provides reference information for topiramate dosage adjustment during pregnancy and helps improve its safety and efficacy in pregnant women and fetuses.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Physiologically Based Pharmacokinetic Modeling to Predict Maternal Pharmacokinetic Changes of Topiramate During Pregnancy and Recommend Dose Adjustments.\",\"authors\":\"Yuying Chen, Meng Ke, Wanhong Wu, Cuihong Lin\",\"doi\":\"10.1002/jcph.70105\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Topiramate is increasingly used in the treatment of epilepsy during pregnancy. However, its plasma concentration evidently decreases during pregnancy, which may reduce its efficacy. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of topiramate to simulate maternal and fetal pharmacokinetic changes across different trimesters and to propose dose adjustments. We established a topiramate pregnancy PBPK model in PK-Sim and Mobi. The model was validated using clinically observed data and subsequently used to optimize the dosage during pregnancy. Simulation results showed that the mean steady-state trough plasma concentration of topiramate decreased by 9.4%, 32%, and 46% in the first, second, and third trimesters, respectively. Based on these findings, the dosage should remain unchanged during the first trimester of pregnancy. However, increasing the baseline dose of topiramate by at least 1.5- and 1.9-fold during the second and third trimesters, respectively, may help maintain effective plasma concentrations. This study provides reference information for topiramate dosage adjustment during pregnancy and helps improve its safety and efficacy in pregnant women and fetuses.</p>\",\"PeriodicalId\":48908,\"journal\":{\"name\":\"Journal of Clinical Pharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/jcph.70105\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/jcph.70105","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

托吡酯越来越多地用于治疗妊娠期癫痫。但妊娠期血药浓度明显降低,可能降低其疗效。本研究旨在建立一个基于生理的托吡酯药代动力学(PBPK)模型,以模拟不同妊娠期母体和胎儿的药代动力学变化,并提出剂量调整建议。在PK-Sim和Mobi中建立托吡酯类妊娠PBPK模型。该模型使用临床观察数据进行验证,并随后用于优化妊娠期间的剂量。模拟结果显示,托吡酯在妊娠第一、第二和第三三个月的平均稳态血药谷浓度分别下降了9.4%、32%和46%。根据这些发现,在怀孕的前三个月,剂量应该保持不变。然而,在妊娠中期和晚期分别将托吡酯的基线剂量增加至少1.5倍和1.9倍,可能有助于维持有效的血药浓度。本研究为妊娠期托吡酯剂量调整提供参考信息,有助于提高托吡酯在孕妇和胎儿中的安全性和有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Physiologically Based Pharmacokinetic Modeling to Predict Maternal Pharmacokinetic Changes of Topiramate During Pregnancy and Recommend Dose Adjustments.

Topiramate is increasingly used in the treatment of epilepsy during pregnancy. However, its plasma concentration evidently decreases during pregnancy, which may reduce its efficacy. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of topiramate to simulate maternal and fetal pharmacokinetic changes across different trimesters and to propose dose adjustments. We established a topiramate pregnancy PBPK model in PK-Sim and Mobi. The model was validated using clinically observed data and subsequently used to optimize the dosage during pregnancy. Simulation results showed that the mean steady-state trough plasma concentration of topiramate decreased by 9.4%, 32%, and 46% in the first, second, and third trimesters, respectively. Based on these findings, the dosage should remain unchanged during the first trimester of pregnancy. However, increasing the baseline dose of topiramate by at least 1.5- and 1.9-fold during the second and third trimesters, respectively, may help maintain effective plasma concentrations. This study provides reference information for topiramate dosage adjustment during pregnancy and helps improve its safety and efficacy in pregnant women and fetuses.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Clinical Pharmacology
Journal of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
自引率
3.40%
发文量
0
期刊介绍: The Journal of Clinical Pharmacology (JCP) is a Human Pharmacology journal designed to provide physicians, pharmacists, research scientists, regulatory scientists, drug developers and academic colleagues a forum to present research in all aspects of Clinical Pharmacology. This includes original research in pharmacokinetics, pharmacogenetics/pharmacogenomics, pharmacometrics, physiologic based pharmacokinetic modeling, drug interactions, therapeutic drug monitoring, regulatory sciences (including unique methods of data analysis), special population studies, drug development, pharmacovigilance, womens’ health, pediatric pharmacology, and pharmacodynamics. Additionally, JCP publishes review articles, commentaries and educational manuscripts. The Journal also serves as an instrument to disseminate Public Policy statements from the American College of Clinical Pharmacology.
×
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:604180095
Book学术官方微信