Pharmacokinetics of the dual melatonin receptor agonist tasimelteon in subjects with hepatic or renal impairment

• Published in: Journal of clinical pharmacology Vol. 55; no. 5; pp. 525 - 533
• Main Authors: Torres, Rosarelis, Kramer, William G., Baroldi, Paolo
• Format: Journal Article
• Language: English
• Published: England 01.05.2015
• Subjects: Adolescent; Adult; Aged; Area Under Curve; Benzofurans - pharmacokinetics; Benzofurans - therapeutic use; Cyclopropanes - pharmacokinetics; Cyclopropanes - therapeutic use; dual melatonin receptor agonists; Female; Half-Life; hepatic function impairment; Humans; Liver Diseases - metabolism; Male; Metabolic Clearance Rate; Middle Aged; pharmacokinetics; Receptors, Melatonin - agonists; Renal Dialysis; renal function impairment; Renal Insufficiency - metabolism; Severity of Illness Index; Sleep Disorders, Circadian Rhythm - drug therapy; tasimelteon; United States; Young Adult; United States; dual melatonin receptor agonists; pharmacokinetics; renal function impairment; hepatic function impairment; tasimelteon
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1002/jcph.440

Tasimelteon is a circadian regulator that resets the master clock in the suprachiasmatic nuclei of the hypothalamus by binding to both melatonin MT1 and MT2 receptors making it a dual melatonin receptor agonist. Tasimelteon has been approved by the United States Food and Drug Administration for the treatment of Non‐24‐Hour Sleep‐Wake Disorder (Non‐24). Two prospective, single‐center, open‐label studies evaluated the pharmacokinetics of tasimelteon and its main metabolites after a single 20 mg dose administered to subjects with mild or moderate hepatic impairment or severe renal impairment, including subjects on dialysis compared to healthy controls. In subjects with mild or moderate hepatic impairment, exposure to tasimelteon after a single 20 mg dose, as measured by area under the plasma concentration‐time curve to infinity, was increased by approximately 2‐fold. There was no apparent relationship between tasimelteon clearance and renal function. No safety concerns were apparent in either study. Based on these results, the changes in the pharmacokinetics of tasimelteon due to mild or moderate hepatic or severe renal impairment are not considered clinically relevant, and no dose adjustment is necessary in these patients.