{"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}
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.
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.