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Often, the two drugs are co\u2010administered to reduce required doses of valproate, a known potential teratogen. This study used Genetic Absence Epilepsy Rat from Strasbourg to evaluate transfer of valproate and lamotrigine across late gestation placenta and their entry into cerebrospinal fluid (CSF) and brain of developing rats, in mono\u2010 and combination therapies. Animals at embryonic day (E) 19, postnatal day (P) 0, 4 and 21, and adults were administered valproate (30\u2009mg\/kg) or lamotrigine (6\u00a0mg\/kg) with their respective [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010tracers, either alone or in combination. In chronic experiments, females consumed valproate\u2010containing diet from 2\u00a0weeks prior to mating until offspring were used at E19 and P0. Drugs were injected 30\u2009min before blood, CSF and brain samples were collected from terminally anaesthetised animals. Radioactivity in samples was measured. In acute monotherapy brain entry of valproate was higher in foetal than postnatal animals, correlating with its plasma protein binding. Brain entry of lamotrigine was not age\u2010dependent. Combination therapy enhanced entry of lamotrigine into the adult brain but had no effects on brain and CSF entry of valproate. Following chronic valproate exposure, placental transfer of valproate decreased in combination therapy; however, foetal brain entry increased. Results suggest that during pregnancy, the use of combination therapy of valproate and lamotrigine may mitigate overall foetal exposure to valproate but potential risks to foetal brain development are less clear.\n                  <\/jats:p>","DOI":"10.1111\/ejn.16452","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T01:38:04Z","timestamp":1720489084000},"page":"4536-4551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of co\u2010administration of lamotrigine on valproate transfer across the placenta and its brain entry in developing Genetic Absence Epilepsy Rats from Strasbourg (GAERS)"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-1116","authenticated-orcid":false,"given":"Fiona","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Neuroscience Central Clinical School Monash University  Melbourne Victoria 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