{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:58:19Z","timestamp":1791352699575,"version":"4.3.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011096","name":"Jazz Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011096","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>American Academy of Sleep Medicine practice parameters designate sodium oxybate (SXB) as a standard of care for cataplexy, excessive daytime sleepiness (EDS), and disrupted night\u2010time sleep in narcolepsy. Recently, a lower\u2010sodium oxybate (LXB) with 92% less sodium than SXB was approved in the United States for the treatment of cataplexy or EDS in patients 7\u00a0years of age and older with narcolepsy. Two phase I, open\u2010label, randomized, single\u2010dose crossover pharmacokinetic studies in healthy adults were conducted. Single 4.5\u2010g oral doses of LXB and SXB were administered in a fasted or fed state. In the fasted state at equivalent oxybate doses, LXB, compared with SXB, had a lower maximum plasma concentration (C<jats:sub>max<\/jats:sub>; study 1 [total aqueous volume, 240\u00a0ml]: 101.8 vs. 135.7\u00a0\u00b5g\/ml; study 2 [60\u00a0ml]: 94.6 vs. 123.0\u00a0\u03bcg\/ml), delayed time to C<jats:sub>max<\/jats:sub> (T<jats:sub>max<\/jats:sub>; study 1: 0.75 vs. 0.5\u00a0h; study 2: 1.0 vs. 0.5\u00a0h), but similar area under the curve (AUC; study 1: AUC<jats:sub>0\u2010t<\/jats:sub>, 235.4 vs. 263.9\u00a0\u03bcg\u2219h\/ml; AUC<jats:sub>0\u2010\u221e<\/jats:sub>, 236.5 vs. 265.2\u00a0\u03bcg\u2219h\/ml; study 2: AUC<jats:sub>0\u2010t<\/jats:sub>, 241.5 vs. 254.7\u00a0\u03bcg\u2219h\/ml; AUC<jats:sub>0\u2010\u221e<\/jats:sub>, 243.1 vs. 256.3\u00a0\u03bcg\u2219h\/ml). Bioequivalence criteria were met for AUC but not C<jats:sub>max<\/jats:sub> (both studies). C<jats:sub>max<\/jats:sub> and AUC were lower under fed than fasted conditions (LXB and SXB); differences between fed versus fasted were smaller for LXB than SXB. These pharmacokinetic differences between LXB and SXB are likely due to the lower sodium content in LXB. Pooled analyses demonstrated that a higher C<jats:sub>max<\/jats:sub> is associated with a higher incidence of nausea and vomiting.<\/jats:p>","DOI":"10.1111\/cts.13087","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T05:51:56Z","timestamp":1623649916000},"page":"2278-2287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pharmacokinetics, bioavailability, and bioequivalence of lower\u2010sodium oxybate in healthy participants in two open\u2010label, randomized, crossover studies"],"prefix":"10.1111","volume":"14","author":[{"given":"Cuiping","family":"Chen","sequence":"first","affiliation":[{"name":"Jazz Pharmaceuticals, Inc Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals, Inc Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Zomorodi","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals, Inc Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Skowronski","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals, Inc Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"International Classification of Sleep Disorders","author":"American Academy of Sleep Medicine","year":"2014"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2014.01.015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/30.12.1705"},{"key":"e_1_2_10_5_1","volume-title":"Xyrem\u00ae (sodium oxybate) oral solution Prescribing Information","year":"2018"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(18)30133-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12780"},{"key":"e_1_2_10_8_1","volume-title":"Why should I limit sodium?","year":"2017"},{"key":"e_1_2_10_9_1","volume-title":"Dietary Reference Intakes for Sodium and Potassium","author":"National Academies of Sciences, Engineering, and Medicine","year":"2019"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304127"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907355"},{"key":"e_1_2_10_12_1","volume-title":"Xywav\u2122 (calcium, magnesium, potassium, and sodium oxybates) oral solution, CIII Prescribing Information","year":"2020"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaa206"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-019-00689-1"},{"key":"e_1_2_10_15_1","volume-title":"Guidance for Industry: Food\u2010Effect Bioavailability and Fed Bioequivalence Studies","year":"2002"},{"key":"e_1_2_10_16_1","volume-title":"Bioanalytical Method Validation: Guidance for Industry","year":"2018"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.641043"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39147.604896.55"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00112.2005"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/53.3.661"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.014852"},{"key":"e_1_2_10_22_1","unstructured":"WangQ LinT AllphinC vanOsdolWW BolgerMB ChenC.Physiologically based pharmacokinetic modeling of oxybate: the role of counter\u2010ions in gastrointestinal absorption of oxybate [poster]. Presented at: Annual AAPS PharmSci 360; October 26\u2010November 5 2020."},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1960.sp006577"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(02)01553-9"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-020-00543-z"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00298.2014"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13087","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:21:58Z","timestamp":1693196518000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/cts.13087"],"URL":"https:\/\/doi.org\/10.1111\/cts.13087","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,25]]},"assertion":[{"value":"2020-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}