{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:07:43Z","timestamp":1788847663451,"version":"build-2803163510"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Topiramate is sometimes used in patients with bipolar disorder (BD), though off-label, warranting therapeutic drug monitoring (TDM) for safety. Guidelines recommend trough-level sampling (12\u201316h post-dose), but random levels are common, complicating interpretation. A tool to convert random topiramate concentrations to a standardized trough equivalent is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To develop and validate a pharmacokinetic (PK) tool for estimating the standardized trough concentration at 14h post-dose (C\n                      <jats:sub>14<\/jats:sub>\n                      ) from a random sample in patients receiving topiramate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A conversion model was derived using a one-compartment model with population PK parameters for immediate-release topiramate (elimination half-life = 25h, time-to-peak = 3h). A conversion coefficient (Kt) table was generated. The tool was validated against 183 paired TDM samples from inpatients with BD on stable topiramate monotherapy, using the measured C\n                      <jats:sub>14<\/jats:sub>\n                      as reference. Reliability, agreement, and accuracy were assessed\n                      <jats:italic>via<\/jats:italic>\n                      intraclass correlation coefficient (ICC), Bland-Altman analysis, and mean absolute percentage error (MAPE).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The tool demonstrated excellent reliability (ICC = 0.92, 95% CI: 0.90\u20130.94) and agreement (mean bias = +0.008\u00a0\u03bcg\/mL). Predictive accuracy was high (MAPE = 6.3%), with 97.3% of estimates having an absolute error &amp;lt;15%. Performance was consistent across pharmacokinetic phases and subgroups (age, dose).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This preliminary PK conversion tool reliably estimates the standardized trough concentration of immediate-release topiramate from random TDM levels. It could potentially aid safety monitoring by improving the interpretation of non-standard samples, though its clinical utility requires prospective external validation and linkage to patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1867058","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:35:05Z","timestamp":1788845705000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of a pharmacokinetic tool to convert random topiramate concentrations to standardized trough levels in bipolar disorder"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuan","family":"Jv","sequence":"first","affiliation":[{"name":"Department of Psychiatry, The Seventh People\u2019s Hospital of Hangzhou (Affiliated Mental Health Center, Zhejiang University School of Medicine)","place":["Hangzhou, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Li","sequence":"additional","affiliation":[{"name":"Qilihe District People\u2019s Hospital","place":["Lanzhou, Gansu Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Liu","sequence":"additional","affiliation":[{"name":"Gansu Provincial Hospital of Traditional Chinese Medicine","place":["Lanzhou, Gansu Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Cao","sequence":"additional","affiliation":[{"name":"Xiaoshan Third People\u2019s Hospital","place":["Hangzhou, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaopeng","family":"Li","sequence":"additional","affiliation":[{"name":"Jiashan County First People\u2019s Hospital","place":["Jiaxing, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxia","family":"Chen","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Shaoxing University of Arts and Sciences","place":["Shaoxing, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jipeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine","place":["Hangzhou, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiezheng","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The Seventh People\u2019s Hospital of Hangzhou (Affiliated Mental Health Center, Zhejiang University School of Medicine)","place":["Hangzhou, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B21","doi-asserted-by":"publisher","first-page":"522947","DOI":"10.1358\/dot.1999.35.1.522947","article-title":"Pharmacokinetics and metabolism of topiramate","volume":"35","author":"Bourgeois","year":"1999","journal-title":"Drug Ther. 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