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Our objective was to characterize lamotrigine pharmacokinetics in PWWE during pregnancy and postpartum along with a control group of nonpregnant women with epilepsy (NPWWE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study was a prospective, observational, 20 site, cohort study conducted in the United States (December 2012 and February 2016). Inclusion criteria included patients aged 14\u201345\u2009years, gestational age &lt;20\u2009weeks at the time of recruitment, IQ &gt;70 points, and receiving lamotrigine. PWWE participated throughout pregnancy and 18\u2009months postpartum with NPWWE having matched visit intervals. Plasma drug and hormone concentrations were measured at each of the seven visits. A population mixed\u2010effects modeling approach was used to describe lamotrigine clearance change.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>221 (170 PWWE, 51 NPWWE) women were included. Baseline apparent clearance (clearance for NPWWE and when not pregnant for PWWE) was identical between the two groups (2.79 L\/hour. with 36% between\u2010subject variability). Two subpopulations were identified in PWWE: ~91% of PWWE had a maximum increase to 275% of baseline clearance with 50% of the maximum increase reached at 12 weeks gestational age and ~9% had no significant change in clearance during gestation. Following delivery, a first\u2010order mono\u2010exponential decline (1.27 weeks<jats:sup>\u22121<\/jats:sup>) in clearance as a function of postpartum week described a return of clearance to baseline. The use of estrogen\u2010based medication and enzyme\u2010inducing antiseizure medications increased nonpregnant clearance by a further 0.33\u2010fold and 0.84\u2010fold, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>During pregnancy, 91% of PWWE experience a 275% change from nonpregnant baseline in lamotrigine clearance whereas the remaining PWWE experience little to no change. Nonpregnant baseline lamotrigine clearance was higher in both PWWE and NPWWE with the administration of oral estrogen\u2010containing medications. Our results are of clinical importance as they indicate a subpopulation without the need for substantial dose changes during pregnancy and a source of potential difference across nonpregnant individuals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.4640","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T05:13:42Z","timestamp":1736226822000},"page":"33-42","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Characterization of lamotrigine disposition changes during and after pregnancy in women with epilepsy"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-5266","authenticated-orcid":false,"given":"Ashwin","family":"Karanam","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota USA"},{"name":"Pfizer Inc  Cambridge Massachusetts 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