{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:35:07Z","timestamp":1790706907074,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,5,24]],"date-time":"2017-05-24T00:00:00Z","timestamp":1495584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Health's NIHR Biomedical Research Centre's"},{"name":"Dr Marvin Weil Epilepsy Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Given that only the free non\u2013protein\u2010bound concentration of an antiepileptic drug (\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      ) crosses the blood\u2013brain barrier, entering the brain and producing an antiepileptic effect, knowledge and measurement of the free drug fraction is important. Such data are sparse, particularly for newer\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      s, and have arisen from the use of disparate methodologies and settings over the past six decades. We report on the protein binding of 25\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      s that are available for clinical use, along with two pharmacologically active metabolites (carbamazepine\u2010epoxide and\n                      <jats:italic>N<\/jats:italic>\n                      \u2010desmethyl clobazam), using standardized methodology and under set conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The protein binding of the various\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      s was undertaken in sera of 278 patients with epilepsy. Separation of the free non\u2013protein\u2010bound component was achieved by using ultracentrifugation (Amicon Centrifree Micropartition System) under set conditions: 500 \u03bcl serum volume; centrifugation at 1,000\n                      <jats:italic>\n                        <jats:bold>g<\/jats:bold>\n                      <\/jats:italic>\n                      for 15 min, and at 25\u00b0C. Free and total\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      concentrations were measured by use of fully validated liquid chromatography\/mass spectroscopy (LC\/MS) techniques.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Gabapentin and pregabalin are non\u2013protein\u2010bound, whereas highly bound\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      s (\u226588%) include clobazam, clonazepam, perampanel, retigabine, stiripentol, tiagabine, and valproic acid as well as the\n                      <jats:italic>N<\/jats:italic>\n                      \u2010desmethyl\u2010clobazam (89%) metabolite. The minimally bound drugs (&lt;22%) include ethosuximide (21.8%), lacosamide (14.0%), levetiracetam (3.4%), topiramate, (19.5%) and vigabatrin (17.1%). Ten of the 25\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      s exhibit moderate protein binding (mean range 27.7\u201374.8%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      These data provide a comprehensive comparison of serum protein binding of all available\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      s including the metabolites, carbamazepine\u2010epoxide and\n                      <jats:italic>N<\/jats:italic>\n                      \u2010desmethyl\u2010clobazam. Knowledge of the free fraction of these\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      s can be used to optimize epilepsy treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.13802","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T12:56:46Z","timestamp":1495717006000},"page":"1234-1243","source":"Crossref","is-referenced-by-count":114,"title":["Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non\u2013protein\u2010bound concentrations"],"prefix":"10.1111","volume":"58","author":[{"given":"Philip N.","family":"Patsalos","sequence":"first","affiliation":[{"name":"Department of Clinical &amp; Experimental Epilepsy NIHR University College London Hospitals Biomedical Research Centre UCL Institute of Neurology London United Kingdom"},{"name":"Chalfont Centre for Epilepsy Chalfont St. Peter 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Hospitals Biomedical Research Centre UCL Institute of Neurology London United Kingdom"},{"name":"Chalfont Centre for Epilepsy Chalfont St. Peter United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neville","family":"Ratnaraj","sequence":"additional","affiliation":[{"name":"Department of Clinical &amp; Experimental Epilepsy NIHR University College London Hospitals Biomedical Research Centre UCL Institute of Neurology London United Kingdom"},{"name":"Chalfont Centre for Epilepsy Chalfont St. Peter United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-9661","authenticated-orcid":false,"given":"Josemir W.","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Clinical &amp; Experimental Epilepsy NIHR University College London Hospitals Biomedical Research Centre UCL Institute of Neurology London United Kingdom"},{"name":"Chalfont Centre for Epilepsy Chalfont St. Peter United 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