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To address these challenges, newer formulations of these AEDs have been developed using unique extended\u2010release (ER) technologies. These technologies extend the dosing interval such that dosing frequency can be minimized, which may improve patient adherence. Available ER formulations have the potential to minimize the spikes in maximum plasma concentrations (C<jats:sub>max<\/jats:sub>) at steady\u2010state that often contribute to AEs during treatment with immediate\u2010release (IR) products. In so doing, tolerability advantages may lead to increased AED effectiveness by improving adherence and allowing higher doses if clinically indicated. Direct PK comparison studies of IR and ER formulations (e.g., carbamazepine, divalproate sodium, lamotrigine, oxcarbazepine, levetiracetam, and phenytoin) have found that dose\u2010normalized ER formulations may or may not be bioequivalent to their IR counterparts, but most ER formulations have a lower fluctuation index ([C<jats:sub>max<\/jats:sub>\u2013C<jats:sub>min<\/jats:sub>]\/C<jats:sub>avg<\/jats:sub>) compared with the IR versions. This results in flatter concentration\u2010time plots. Not all ER preparations improve the various PK parameters to the same extent, and PK nuances may impact the effectiveness, tolerability, and adherence rates of various ER formulations.<\/jats:p>","DOI":"10.1111\/epi.12043","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T01:48:08Z","timestamp":1354153688000},"page":"28-35","source":"Crossref","is-referenced-by-count":53,"title":["Extended\u2010release antiepileptic drugs: A comparison of pharmacokinetic parameters relative to original immediate\u2010release formulations"],"prefix":"10.1111","volume":"54","author":[{"given":"Ilo E.","family":"Leppik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin A.","family":"Hovinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.03.003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200721090-00005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2006.10.008"},{"key":"e_1_2_7_5_1","first-page":"145","article-title":"Efficacy, safety, and potential of extended\u2010release lamotrigine in the treatment of epileptic patients","volume":"6","author":"Blaszczyk B","year":"2010","journal-title":"Neuropsychiatr Dis Treat"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1990.tb01579.x"},{"key":"e_1_2_7_7_1","unstructured":"Center for Drug Evaluation and Research(2003)Guidance for industry \u2013 bioavailability and bioequivalence studies for orally administered drug products \u2013 general considerations. 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