
Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
Author(s) -
Chen Cuiping,
Jenkins Jack,
Zomorodi Katie,
Skowronski Roman
Publication year - 2021
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.13087
Subject(s) - bioequivalence , cmax , crossover study , pharmacokinetics , medicine , cataplexy , narcolepsy , bioavailability , area under the curve , pharmacology , modafinil , placebo , alternative medicine , pathology
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‐time sleep in narcolepsy. Recently, a lower‐sodium oxybate (LXB) with 92% less sodium than SXB was approved in the United States for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. Two phase I, open‐label, randomized, single‐dose crossover pharmacokinetic studies in healthy adults were conducted. Single 4.5‐g 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 max ; study 1 [total aqueous volume, 240 ml]: 101.8 vs. 135.7 µg/ml; study 2 [60 ml]: 94.6 vs. 123.0 μg/ml), delayed time to C max (T max ; study 1: 0.75 vs. 0.5 h; study 2: 1.0 vs. 0.5 h), but similar area under the curve (AUC; study 1: AUC 0‐t , 235.4 vs. 263.9 μg∙h/ml; AUC 0‐∞ , 236.5 vs. 265.2 μg∙h/ml; study 2: AUC 0‐t , 241.5 vs. 254.7 μg∙h/ml; AUC 0‐∞ , 243.1 vs. 256.3 μg∙h/ml). Bioequivalence criteria were met for AUC but not C max (both studies). C max 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 max is associated with a higher incidence of nausea and vomiting.