{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:16:07Z","timestamp":1786976167422,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Despite the suggested topiramate serum level of 5\u201320\u2009mg\/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as \u201cinsufficient\u201d or \u201csufficient\u201d by reduction in seizure frequency\u2009\u2265\u200950%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 389 epilepsy patients were reviewed having a mean dose of 178.4\u2009\u00b1\u2009117.9\u2009mg\/day and the serum level, 3.9\u2009\u00b1\u20092.8\u2009mg\/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6\u2009\u00b1\u20092.5\u2009mg\/L while 94.4% demonstrated sufficient response, with a mean 4.0\u2009\u00b1\u20092.8\u2009mg\/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04), with an optimal cutoff value of 6.5\u2009mg\/L.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5\u2009mg\/L to mitigate the risk of ataxia\u2010related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51962","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T01:46:17Z","timestamp":1701999977000},"page":"424-435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1285-1334","authenticated-orcid":false,"given":"Seolah","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation Biomedical Research Institute, Seoul National University College of Medicine and Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8819-4780","authenticated-orcid":false,"given":"Hyun Chul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul South Korea"},{"name":"Integrated Major in Innovative Medical Science Seoul National University Graduate School  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-3357","authenticated-orcid":false,"given":"Yoonhyuk","family":"Jang","sequence":"additional","affiliation":[{"name":"Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation Biomedical Research Institute, Seoul National University College of Medicine and Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2881-0366","authenticated-orcid":false,"given":"Han Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation Biomedical Research Institute, Seoul National University College of Medicine and Hospital  Seoul South Korea"},{"name":"Center for Hospital Medicine Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0520-7812","authenticated-orcid":false,"given":"Seon\u2010Jae","family":"Ahn","sequence":"additional","affiliation":[{"name":"Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation Biomedical Research Institute, Seoul National University College of Medicine and Hospital  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