{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T12:15:30Z","timestamp":1780143330272,"version":"3.54.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T00:00:00Z","timestamp":1437609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"FDA","award":["HHSF223201010144A"],"award-info":[{"award-number":["HHSF223201010144A"]}]},{"name":"University of Maryland Clinical Translational Science Institute"},{"name":"University of Maryland General Clinical Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To test the current U.S. Food and Drug Administration (<jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content>) bioequivalence standard in a comparison of generic and brand\u2010name drug pharmacokinetic (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) performance in \u201cgeneric\u2010brittle\u201d patients with epilepsy under clinical use conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, double\u2010blind, multiple\u2010dose, steady\u2010state, fully replicated bioequivalence study compared generic lamotrigine to brand\u2010name <jats:styled-content style=\"fixed-case\">Lamictal<\/jats:styled-content> in \u201cgeneric\u2010brittle\u201d patients with epilepsy (n\u00a0=\u00a034) who were already taking lamotrigine. Patients were repeatedly switched between masked <jats:styled-content style=\"fixed-case\">Lamictal<\/jats:styled-content> and generic lamotrigine. Intensive <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> blood sampling at the end of each 2\u2010week treatment period yielded two 12\u2010h <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> profiles for brand\u2010name and generic forms for each patient. Steady\u2010state area under the curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>), peak plasma concentration (C<jats:sub>max<\/jats:sub>), and minimum plasma concentration (C<jats:sub>min<\/jats:sub>) data were subjected to conventional average bioequivalence (<jats:styled-content style=\"fixed-case\">ABE<\/jats:styled-content>) analysis, reference\u2010scaled <jats:styled-content style=\"fixed-case\">ABE<\/jats:styled-content> analysis, and within\u2010subject variability (<jats:styled-content style=\"fixed-case\">WSV<\/jats:styled-content>) comparisons. In addition, generic\u2010versus\u2010brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady\u2010state <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>, C<jats:sub>max<\/jats:sub>, and C<jats:sub>min<\/jats:sub> for generic\u2010versus\u2010brand were 97.2\u2013101.6%, 98.8\u2013104.5%, and 93.4\u2013101.0%, respectively. The <jats:styled-content style=\"fixed-case\">WSV<\/jats:styled-content> of generic and brand were also similar. Individual patient PK ratios for generic\u2010versus\u2010brand were similar but not identical, in part because brand\u2010versus\u2010brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand\u2010to\u2010generic switching. Bioequivalence results in \u201cgeneric\u2010brittle\u201d patients with epilepsy under clinical conditions support the soundness of the <jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content> bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13095","type":"journal-article","created":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T09:12:50Z","timestamp":1437642770000},"page":"1415-1424","source":"Crossref","is-referenced-by-count":63,"title":["Generic lamotrigine versus brand\u2010name <scp>Lamictal<\/scp> bioequivalence in patients with epilepsy: A field test of the <scp>FDA<\/scp> bioequivalence standard"],"prefix":"10.1111","volume":"56","author":[{"given":"Tricia Y.","family":"Ting","sequence":"first","affiliation":[{"name":"Department of Neurology University of Maryland Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Food and Drug Administration White Oak Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lionberger","sequence":"additional","affiliation":[{"name":"Food and Drug Administration White Oak Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jace W.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen A.","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Krumholz","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Maryland Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Temple","sequence":"additional","affiliation":[{"name":"Food and Drug Administration White Oak Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Polli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1086-5802(16)31327-4"},{"key":"e_1_2_8_3_1","unstructured":"IMS Institute for Healthcare Informatics.Medicine Use and Shifting Costs of Healthcare: A Review of the Use of Medicines in the United States in 2013. 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