{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:35:48Z","timestamp":1784183748465,"version":"3.55.0"},"reference-count":16,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001605","name":"Epilepsy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001605","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD105305"],"award-info":[{"award-number":["R01HD105305"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Maintaining seizure control with lamotrigine is complicated by altered pharmacokinetics and existence of subpopulations in whom clearance increases or remains constant during pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our objective was to characterize the potential for particular dosing scenarios to lead to increased seizure risk or toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lamotrigine pharmacokinetic parameters obtained from our previous study were applied to a one\u2010compartment model structure with subpopulations (75:25%) exhibiting different clearance changes. A single\u2010patient simulation was conducted with typical pharmacokinetic parameter values from each subpopulation. Population\u2010level simulations (<jats:italic>N<\/jats:italic>\u2009=\u200948,000) included six dosing scenarios and considered four preconception doses using the R package mrgsolve (Metrum Research Group). Thresholds for efficacy and toxicity were selected as drug concentration that are 65% lower than preconception concentrations and doubling of preconception concentrations, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Individual simulation results demonstrated that without dose increases, concentrations fell below 0.65 at 6\u20138\u2009weeks in the high clearance change (HC) subpopulation, depending on preconception clearance. While no simulated dosing regimen allowed all women in both subpopulations to maintain preconception concentrations, some regimens provided a more balanced risk profile than others. Predicted concentrations suggested potential increased seizure risk for 7%\u2013100% of women in the HC group depending on preconception dose and subpopulation. Additionally, in 63% of dosing scenarios for women with low clearance change (LC), there was an increased risk of toxicity (34%\u2013100% of women).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>A substantial percentage of simulated individuals had concentrations low enough to potentially increase seizure risk or high enough to create toxicity. Early clearance changes indicate possible subpopulation categorization if therapeutic drug monitoring is conducted in the first trimester. An arbitrary \u201cone\u2010size\u2010fits\u2010all\u201d philosophy may not work well for lamotrigine dosing adjustments during pregnancy and reinforces the need for therapeutic drug monitoring until a patient is determined to be in the LC or HC group.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2856","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T01:54:42Z","timestamp":1689904482000},"page":"998-1006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Empiric dosing strategies to predict lamotrigine concentrations during pregnancy"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-5650","authenticated-orcid":false,"given":"Jessica M.","family":"Barry","sequence":"first","affiliation":[{"name":"Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8027","authenticated-orcid":false,"given":"Jacqueline A.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Comprehensive Epilepsy Center New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0568-2795","authenticated-orcid":false,"given":"Page B.","family":"Pennell","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin","family":"Karanam","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia L.","family":"Harden","sequence":"additional","affiliation":[{"name":"Xenon Pharmaceuticals, Inc. Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3969-4906","authenticated-orcid":false,"given":"Angela K.","family":"Birnbaum","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology, College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2015.1083422"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-017-0433-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30107-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70323-X"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000289511.20864.2a"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.06.026"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.29"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25321"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2011.01627.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a6b325"},{"key":"e_1_2_8_12_1","unstructured":"PennellPB McElrathT.Management of epilepsy during preconception pregnancy and the postpartum period. UpToDate [Internet]2021https:\/\/www.uptodate.com\/contents\/management\u2010of\u2010epilepsy\u2010during\u2010preconception\u2010pregnancy\u2010and\u2010the\u2010postpartum\u2010period"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2111"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1997.00594.x"},{"key":"e_1_2_8_15_1","volume-title":"Mrgsolve. 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