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Published data on the pharmacokinetics of memantine in the mouse are still incomplete, particularly for chronic administration regimens and mouse models of specific genetic disorders. Down's syndrome (<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>) is a genetic disorder known to affect multiple organs and systems, with the potential to alter significantly drug pharmacokinetics. Here, we describe a simple, efficient and sensitive <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\u2010based procedure for the determination of memantine concentrations in murine blood and tissue samples. We analysed pharmacokinetic properties of memantine, particularly its distribution in blood, brain and liver in the Ts65Dn mouse model of <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> and euploid F1 hybrid mice after single intraperitoneal administrations of increasing doses of this drug. We also determined steady\u2010state memantine concentrations in plasma, brain and liver after chronic oral administration of this drug in adult male Ts65Dn mice, euploid littermate controls and nursing or pregnant Ts65Dn mice. Our results revalidated the acute dose of memantine used in previously published work, determined the appropriate amount of memantine to be mixed into mouse chow to achieve steady and pharmacologically relevant plasma and tissue levels of this drug and demonstrated that memantine can be transferred from mother to offspring via maternal milk and placenta. Most of these findings are potentially applicable not only to the study of <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> but also to other neurodevelopmental and neurodegenerative disorders.<\/jats:p>","DOI":"10.1111\/bcpt.12816","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T13:51:38Z","timestamp":1496152298000},"page":"382-389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacokinetic Properties of Memantine after a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down's Syndrome"],"prefix":"10.1111","volume":"121","author":[{"given":"Daniella B.","family":"Victorino","sequence":"first","affiliation":[{"name":"Division of Neurology and Epilepsy Department of Pediatrics Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya R.","family":"Bederman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto C. S.","family":"Costa","sequence":"additional","affiliation":[{"name":"Division of Neurology and Epilepsy Department of Pediatrics Case Western Reserve University Cleveland OH USA"},{"name":"Department of Psychiatry Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.07.013"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2004.05.005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2003.tb00254.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1958"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0809-1"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.10.007"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199403033300907"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000081061.12235.55"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.11.013"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152707781387279"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858404269012"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.187"},{"key":"e_1_2_6_14_1","first-page":"41","article-title":"Le Mongolisme premier exemple daberration autosomique humaine","volume":"1","author":"Lejeune J","year":"1959","journal-title":"Ann Genet\u2010Paris"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1525"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/18715273113126660183"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.66"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61676-0"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.40"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-011-9356-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2144\/000114373"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301535"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000332829"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/101249"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.303"},{"key":"e_1_2_6_26_1","first-page":"1471","article-title":"[Gaschromatographic and mass spectrometric studies on metabolites of adamantane amines excreted with urine (author's transl)]","volume":"27","author":"Wesemann W","year":"1977","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12479"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.071027"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1291"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.07.042"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.03.036"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.01.012"},{"key":"e_1_2_6_33_1","unstructured":"EPAR. 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