Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies

Abstract 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 t...

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Autores principales:	Cuiping Chen, Jack Jenkins, Katie Zomorodi, Roman Skowronski
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/59ff0e857edc4273b36d35215aba5764
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spelling	oai:doaj.org-article:59ff0e857edc4273b36d35215aba57642021-11-19T17:51:35ZPharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies1752-80621752-805410.1111/cts.13087https://doaj.org/article/59ff0e857edc4273b36d35215aba57642021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13087https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract 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 (Cmax; 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 Cmax (Tmax; 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: AUC0‐t, 235.4 vs. 263.9 μg∙h/ml; AUC0‐∞, 236.5 vs. 265.2 μg∙h/ml; study 2: AUC0‐t, 241.5 vs. 254.7 μg∙h/ml; AUC0‐∞, 243.1 vs. 256.3 μg∙h/ml). Bioequivalence criteria were met for AUC but not Cmax (both studies). Cmax 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 Cmax is associated with a higher incidence of nausea and vomiting.Cuiping ChenJack JenkinsKatie ZomorodiRoman SkowronskiWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2278-2287 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Cuiping Chen Jack Jenkins Katie Zomorodi Roman Skowronski Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
description	Abstract 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 (Cmax; 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 Cmax (Tmax; 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: AUC0‐t, 235.4 vs. 263.9 μg∙h/ml; AUC0‐∞, 236.5 vs. 265.2 μg∙h/ml; study 2: AUC0‐t, 241.5 vs. 254.7 μg∙h/ml; AUC0‐∞, 243.1 vs. 256.3 μg∙h/ml). Bioequivalence criteria were met for AUC but not Cmax (both studies). Cmax 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 Cmax is associated with a higher incidence of nausea and vomiting.
format	article
author	Cuiping Chen Jack Jenkins Katie Zomorodi Roman Skowronski
author_facet	Cuiping Chen Jack Jenkins Katie Zomorodi Roman Skowronski
author_sort	Cuiping Chen
title	Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
title_short	Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
title_full	Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
title_fullStr	Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
title_full_unstemmed	Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
title_sort	pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/59ff0e857edc4273b36d35215aba5764
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Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies

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