Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment

Abstract The aim of this study was to evaluate the impact of renal impairment on the pharmacokinetics (PKs), safety, and tolerability of daridorexant, a dual orexin receptor antagonist intended for the treatment of insomnia. A single‐center, open‐label study evaluated the PKs of daridorexant in pati...

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Autores principales:	Benjamin Berger, Clemens Muehlan, Gernot Klein, Jasper Dingemanse
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/fc8b4cfe396c4a1ebd06e4c57683c6a4
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spelling	oai:doaj.org-article:fc8b4cfe396c4a1ebd06e4c57683c6a42021-11-19T17:51:34ZPharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment1752-80621752-805410.1111/cts.13079https://doaj.org/article/fc8b4cfe396c4a1ebd06e4c57683c6a42021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13079https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract The aim of this study was to evaluate the impact of renal impairment on the pharmacokinetics (PKs), safety, and tolerability of daridorexant, a dual orexin receptor antagonist intended for the treatment of insomnia. A single‐center, open‐label study evaluated the PKs of daridorexant in patients with severe renal function impairment (SRFI; determined by creatinine clearance using the Cockcroft‐Gault equation; N = 8) not on dialysis, and in matched control subjects (based on sex, age, and body weight; N = 7). A single oral dose of daridorexant 25 mg was orally administered in the morning. Blood samples were collected up to 72 h postdose for PK assessments of daridorexant. In patients with SRFI, maximum plasma concentrations (Cmax; geometric mean ratio [GMR] and 90% confidence interval [CI]: 0.94 [0.60–1.46]), time to reach Cmax (Tmax; median difference [90% CI] of −0.25 h [−0.75 to 0.25]), and half‐life (GMR [90% CI] of 0.99 [0.66–1.48]), were virtually unchanged. Exposure (area under the plasma concentration‐time profile) to daridorexant was slightly higher in patients with SRFI than in control subjects with the GMR (90% CI) being 1.16 (0.63–2.12). No safety issue of concern was detected as all adverse events were transient and of mild or moderate intensity, and no treatment‐related effects on vital signs, clinical laboratory, or electrocardiogram variables were observed following daridorexant administration in patients with SRFI and control subjects. Based on these observations, PK alterations of daridorexant due to renal function impairment are not considered of clinical relevance and no dose adjustment is necessary in these patients.Benjamin BergerClemens MuehlanGernot KleinJasper DingemanseWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2132-2138 (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 Benjamin Berger Clemens Muehlan Gernot Klein Jasper Dingemanse Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment
description	Abstract The aim of this study was to evaluate the impact of renal impairment on the pharmacokinetics (PKs), safety, and tolerability of daridorexant, a dual orexin receptor antagonist intended for the treatment of insomnia. A single‐center, open‐label study evaluated the PKs of daridorexant in patients with severe renal function impairment (SRFI; determined by creatinine clearance using the Cockcroft‐Gault equation; N = 8) not on dialysis, and in matched control subjects (based on sex, age, and body weight; N = 7). A single oral dose of daridorexant 25 mg was orally administered in the morning. Blood samples were collected up to 72 h postdose for PK assessments of daridorexant. In patients with SRFI, maximum plasma concentrations (Cmax; geometric mean ratio [GMR] and 90% confidence interval [CI]: 0.94 [0.60–1.46]), time to reach Cmax (Tmax; median difference [90% CI] of −0.25 h [−0.75 to 0.25]), and half‐life (GMR [90% CI] of 0.99 [0.66–1.48]), were virtually unchanged. Exposure (area under the plasma concentration‐time profile) to daridorexant was slightly higher in patients with SRFI than in control subjects with the GMR (90% CI) being 1.16 (0.63–2.12). No safety issue of concern was detected as all adverse events were transient and of mild or moderate intensity, and no treatment‐related effects on vital signs, clinical laboratory, or electrocardiogram variables were observed following daridorexant administration in patients with SRFI and control subjects. Based on these observations, PK alterations of daridorexant due to renal function impairment are not considered of clinical relevance and no dose adjustment is necessary in these patients.
format	article
author	Benjamin Berger Clemens Muehlan Gernot Klein Jasper Dingemanse
author_facet	Benjamin Berger Clemens Muehlan Gernot Klein Jasper Dingemanse
author_sort	Benjamin Berger
title	Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment
title_short	Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment
title_full	Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment
title_fullStr	Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment
title_full_unstemmed	Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment
title_sort	pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/fc8b4cfe396c4a1ebd06e4c57683c6a4
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Pharmacokinetics of daridorexant, a dual orexin receptor antagonist, are not affected by renal impairment

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