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Patients with significant cardiac disease, severe kidney dysfunction, or moderate\u2010to\u2010severe liver dysfunction were excluded. Fifty milligrams of a stable\u2010labeled intravenous <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> formulation (<jats:styled-content style=\"fixed-case\">SL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content>) replaced 50\u00a0mg of a patient's normal daily oral <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> dose. Thirteen blood samples were collected in each person over 96\u00a0hours. <jats:styled-content style=\"fixed-case\">SL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> and unlabeled <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> concentrations were measured simultaneously by gas chromatography\u2013mass spectrometry. Concentration\u2010time data were analyzed by nonlinear mixed\u2010effects modeling (<jats:styled-content style=\"fixed-case\">NONMEM<\/jats:styled-content> version 7.3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010eight patients representing 16 young (18\u201048\u00a0years old) and 12 elderly (63\u201087\u00a0years old) patients were included, yielding 382 unlabeled and 351 <jats:styled-content style=\"fixed-case\">SL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> concentrations. A two\u2010compartment model with first\u2010order absorption and elimination adequately described the plasma concentration\u2010time data. Bioavailability of oral <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> was approximately 74% and did not differ by age. <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> clearance was 27.2% lower in elderly than in young patients (1.80\u00a0L\/h for a 70\u2010kg patient).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Although <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> bioavailability was not affected by age, <jats:styled-content style=\"fixed-case\">LTG<\/jats:styled-content> clearance was 27.2% lower in elderly versus young patients of comparable body weight, possibly indicating lower dosages being needed in this population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14519","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T06:38:46Z","timestamp":1534142326000},"page":"1718-1726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Lamotrigine pharmacokinetics following oral and stable\u2010labeled intravenous administration in young and elderly adult epilepsy patients: Effect of age"],"prefix":"10.1111","volume":"59","author":[{"given":"Akshanth R.","family":"Polepally","sequence":"first","affiliation":[{"name":"Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Brundage","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rory P.","family":"Remmel","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota"},{"name":"Department of Medicinal Chemistry College of Pharmacy, University of Minnesota Minneapolis Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilo E.","family":"Leppik","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Page B.","family":"Pennell","sequence":"additional","affiliation":[{"name":"Department of Neurology at Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"White","sequence":"additional","affiliation":[{"name":"MINCEP Epilepsy Care Minneapolis Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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