{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(2)"],"submitter":["Landry I"],"pubmed_abstract":["The primary aim of this study was to examine the effect of severe renal impairment (SRI) on the pharmacokinetics of lemborexant, a dual orexin receptor antagonist indicated for the treatment of insomnia. A phase 1 multicenter, single-dose, open-label, parallel-group study was conducted in subjects with SRI not requiring dialysis (estimated glomerular filtration rate 15-29 ml/min/1.73 m<sup>2</sup> ; n = 8) compared with demographically matched healthy subjects with normal renal function (n = 8). Plasma levels of lemborexant and its metabolites were measured over 240 h following a single oral 10-mg dose administered in the morning. Relative to subjects with normal renal function, lemborexant maximum plasma concentration (C<sub>max</sub> ) was similar, whereas area under the plasma concentration-time curve from zero to time of last quantifiable concentration (AUC<sub>(0-</sub> <sub>t</sub> <sub>)</sub> ) and AUC from zero to infinity (AUC<sub>(0-inf)</sub> ) were about 1.5-fold higher in subjects with SRI. The geometric mean ratios (90% confidence interval) were 104.8 (77.4-142.0), 150.5 (113.2-200.3), and 149.8 (113.1-198.6) for C<sub>max</sub> , AUC<sub>(0-</sub> <sub>t</sub> <sub>)</sub> , and AUC<sub>(0-inf)</sub> , respectively. In both groups, the median lemborexant time to C<sub>max</sub> (t<sub>max</sub> ) was 1 h, and the mean unbound fraction of lemborexant was ~7%. For the M4, M9, and M10 metabolites, C<sub>max</sub> was reduced ~20% and exposure (AUC<sub>(0-</sub> <sub>t</sub> <sub>)</sub> and AUC<sub>(0-inf)</sub> ) was ~1.4- to 1.5-fold higher in subjects with SRI versus healthy subjects; t<sub>max</sub> was delayed ~1.5-2 h for M4 and M10. All treatment-emergent adverse events were mild or moderate. Lemborexant pharmacokinetics were not sufficiently altered to warrant a dose adjustment for subjects with renal impairment."],"journal":["Pharmacology research & perspectives"],"pagination":["e00734"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7945683"],"repository":["biostudies-literature"],"pubmed_title":["Effect of severe renal impairment on pharmacokinetics, safety, and tolerability of lemborexant."],"pmcid":["PMC7945683"],"pubmed_authors":["Hall N","Moline M","Landry I","Aluri J","Filippov G","Dayal S","Reyderman L"],"additional_accession":[]},"is_claimable":false,"name":"Effect of severe renal impairment on pharmacokinetics, safety, and tolerability of lemborexant.","description":"The primary aim of this study was to examine the effect of severe renal impairment (SRI) on the pharmacokinetics of lemborexant, a dual orexin receptor antagonist indicated for the treatment of insomnia. A phase 1 multicenter, single-dose, open-label, parallel-group study was conducted in subjects with SRI not requiring dialysis (estimated glomerular filtration rate 15-29 ml/min/1.73 m<sup>2</sup> ; n = 8) compared with demographically matched healthy subjects with normal renal function (n = 8). Plasma levels of lemborexant and its metabolites were measured over 240 h following a single oral 10-mg dose administered in the morning. Relative to subjects with normal renal function, lemborexant maximum plasma concentration (C<sub>max</sub> ) was similar, whereas area under the plasma concentration-time curve from zero to time of last quantifiable concentration (AUC<sub>(0-</sub> <sub>t</sub> <sub>)</sub> ) and AUC from zero to infinity (AUC<sub>(0-inf)</sub> ) were about 1.5-fold higher in subjects with SRI. The geometric mean ratios (90% confidence interval) were 104.8 (77.4-142.0), 150.5 (113.2-200.3), and 149.8 (113.1-198.6) for C<sub>max</sub> , AUC<sub>(0-</sub> <sub>t</sub> <sub>)</sub> , and AUC<sub>(0-inf)</sub> , respectively. In both groups, the median lemborexant time to C<sub>max</sub> (t<sub>max</sub> ) was 1 h, and the mean unbound fraction of lemborexant was ~7%. For the M4, M9, and M10 metabolites, C<sub>max</sub> was reduced ~20% and exposure (AUC<sub>(0-</sub> <sub>t</sub> <sub>)</sub> and AUC<sub>(0-inf)</sub> ) was ~1.4- to 1.5-fold higher in subjects with SRI versus healthy subjects; t<sub>max</sub> was delayed ~1.5-2 h for M4 and M10. All treatment-emergent adverse events were mild or moderate. Lemborexant pharmacokinetics were not sufficiently altered to warrant a dose adjustment for subjects with renal impairment.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2025-04-03T21:33:50.111Z","creation":"2025-04-03T21:33:50.111Z"},"accession":"S-EPMC7945683","cross_references":{"pubmed":["33689224"],"doi":["10.1002/prp2.734"]}}