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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-11-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13087 |
| _version_ | 1819320460717850624 |
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| author | Cuiping Chen Jack Jenkins Katie Zomorodi Roman Skowronski |
| author_facet | Cuiping Chen Jack Jenkins Katie Zomorodi Roman Skowronski |
| author_sort | Cuiping Chen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-24T11:19:56Z |
| format | Article |
| id | doaj.art-59ff0e857edc4273b36d35215aba5764 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-12-24T11:19:56Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-59ff0e857edc4273b36d35215aba57642022-12-21T16:58:16ZengWileyClinical and Translational Science1752-80541752-80622021-11-011462278228710.1111/cts.13087Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studiesCuiping Chen0Jack Jenkins1Katie Zomorodi2Roman Skowronski3Jazz Pharmaceuticals, Inc Palo Alto California USAJazz Pharmaceuticals, Inc Palo Alto California USAJazz Pharmaceuticals, Inc Palo Alto California USAJazz Pharmaceuticals, Inc Palo Alto California USAAbstract 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.https://doi.org/10.1111/cts.13087 |
| spellingShingle | 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 Clinical and Translational Science |
| title | 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_short | 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 |
| url | https://doi.org/10.1111/cts.13087 |
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