ArticleClinical pharmacokinetics2021
Effect of Liver Cirrhosis on the Pharmacokinetics, Metabolism, and Tolerability of Daridorexant, A Novel Dual Orexin Receptor Antagonist.
Article in Clinical pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03713242 (A Single-center, Open-label, Single-dose, Phase 1 Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment), which is not on this map. Cited by 13 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Single-center, Open-label, Single-dose, Phase 1 Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment
Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Matching in Organ Impairment Studies: A Systematic Review of Accepted Methodologies.The AAPS journal · 2025Pooled it
- Re-discover the value of protein binding assessments in hepatic and renal impairment studies and its contributions in drug labels and dose decisions.Clinical and translational science · 2024Pooled it
- Long-Term Safety and Tolerability of Daridorexant in Patients with Insomnia Disorder.CNS drugs · 2023Trial
- Personalized prognosis in unresectable hepatocellular carcinoma: Development and validation of a model for transcatheter arterial chemoembolization plus lenvatinib.World journal of gastrointestinal oncology · 2025Article
- New Insights Into Hepatic Impairment (HI) Trials.Clinical and translational science · 2025Review
- Emerging and upcoming therapies in insomnia.Translational and clinical pharmacology · 2024Article
- Daridorexant in Insomnia Disorder: A Profile of Its Use.CNS drugs · 2023Article
- Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations.Nature and science of sleep · 2023Review
- Daridorexant for the treatment of insomnia disorder: findings and implications.European journal of clinical pharmacology · 2022Review
- Daridorexant: A New Dual Orexin Receptor Antagonist for Insomnia.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2022Review
- A Comprehensive Review of Daridorexant, a Dual-Orexin Receptor Antagonist as New Approach for the Treatment of Insomnia.Molecules (Basel, Switzerland) · 2022Review
- Liver Cirrhosis Affects the Pharmacokinetics of the Six Substrates of the Basel Phenotyping Cocktail Differently.Clinical pharmacokinetics · 2022Article
- Daridorexant: First Approval.Drugs · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveDaridorexant is a dual orexin receptor antagonist in clinical development for insomnia. As daridorexant is cleared mainly via cytochrome P450 (CYP) 3A4, the effect of hepatic impairment on the pharmacokinetics (PK), metabolism, and tolerability of daridorexant was evaluated. Sleep disorders are common in patients with liver cirrhosis and, therefore, sleep-promoting drugs with a better tolerability than currently available would be preferable, a premise that dual orexin receptor antagonists may fulfill.
methodsThis was a single-dose, open-label, phase I study. Subjects with mild (Child-Pugh A, N = 8) or moderate (Child-Pugh B, N = 8) liver cirrhosis and matched healthy control subjects (N = 8) received 25 mg of daridorexant orally. Blood samples were collected for 72 h post-dose for PK assessments of daridorexant and three major metabolites.
resultsCompared with healthy subjects, patients showed a decrease in total daridorexant area under the plasma concentration-time curve from zero to infinity (AUC
conclusionsNo safety issue of concern was detected following administration of 25 mg of daridorexant in the study population. Moderate liver cirrhosis causes impaired hepatic clearance of unbound daridorexant, which prolongs the half-life. A 25-mg dose of daridorexant should, therefore, not be exceeded in Child-Pugh B patients. A dose adjustment is not required in Child-Pugh A patients, while avoidance of daridorexant in patients with Child-Pugh C cirrhosis is recommended. CLINICAL
trial registrationClinicalTrials.gov ID: NCT03713242.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.