{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:56:16Z","timestamp":1771937776111,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T00:00:00Z","timestamp":1371168000000},"content-version":"vor","delay-in-days":164,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Gabapentin enacarbil (GEn) is an actively transported prodrug of gabapentin that provides sustained dose\u2010proportional exposure to gabapentin and predictable bioavailability. Gabapentin enacarbil is approved by the US Food and Drug Administration for the treatment of moderate\u2010to\u2010severe primary restless legs syndrome (RLS) in adults. Using plasma gabapentin concentration data obtained after administration of GEn in 12 phase 1 to 3 GEn studies in healthy adults or patients with RLS (dose range, 300\u20102400 mg\/d), a population pharmacokinetic (PK) model was developed by nonlinear mixed\u2010effect modeling using NONMEM. Data were similar in subjects with and without RLS. Population PK\u2010pharmacodynamic (PD) models were evaluated using gabapentin exposure and change from baseline in investigator\u2010 or patient\u2010rated Clinical Global Impression of Improvement (CGI\u2010I) or International Restless Legs Scale (IRLS) total score. Potential PK\u2010PD models for sleep outcomes and safety parameters were also explored. The CGI\u2010I response increased with increasing GEn dose, whereas the IRLS total score was similar at all exposures tested. Early adverse events of dizziness or somnolence\/sedation were more frequent for GEn 600 mg than higher doses; however, this is confounded by the fact that all subjects received the 600\u2010mg dose for 3 days prior to titration to higher dosages.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0091270012439209","type":"journal-article","created":{"date-parts":[[2012,3,16]],"date-time":"2012-03-16T05:06:38Z","timestamp":1331874398000},"page":"29-40","source":"Crossref","is-referenced-by-count":21,"title":["Population Pharmacokinetics and Pharmacodynamics of Gabapentin After Administration of Gabapentin Enacarbil"],"prefix":"10.1002","volume":"53","author":[{"given":"Ritu","family":"Lal","sequence":"first","affiliation":[{"name":"XenoPort, Inc  Santa Clara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juthamas","family":"Sukbuntherng","sequence":"additional","affiliation":[{"name":"Pharmacyclics, Inc  Sunnyvale, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Luo","sequence":"additional","affiliation":[{"name":"XenoPort, Inc  Santa Clara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Tovera","sequence":"additional","affiliation":[{"name":"XenoPort, Inc  Santa Clara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie Liesse","family":"Lassauzet","sequence":"additional","affiliation":[{"name":"XenoPort, Inc  Santa Clara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth C.","family":"Cundy","sequence":"additional","affiliation":[{"name":"XenoPort, Inc  Santa Clara, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,6,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.067959"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.067934"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008322909"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2009.07.026"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03616.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/32.2.159"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000341770.91926.cc"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1389-9457(03)00010-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2004.03.006"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.9.1393"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2003.07.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/WNF.0b013e31820d6699","article-title":"The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome","volume":"34","author":"Dang D","year":"2011","journal-title":"Clin Neuropharmacol"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.294"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2010.07.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018951214146"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2011.12.004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e3181b3ab16"},{"key":"e_1_2_8_19_1","article-title":"A randomized, double\u2010blind, placebo\u2010controlled, dose\u2010response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome","author":"Lal R","journal-title":"Clin Neuropharmacol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7090282"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2009.0700"},{"key":"e_1_2_8_22_1","unstructured":"World Medical Association. 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