Pharmacokinetics of the dual melatonin receptor agonist tasimelteon in subjects with hepatic or renal impairment
| Autor: | William G. Kramer, Paolo Baroldi, Rosarelis Torres |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Cyclopropanes Male medicine.medical_specialty hepatic function impairment Adolescent Metabolic Clearance Rate medicine.medical_treatment Receptors Melatonin Renal function Pharmacology Severity of Illness Index Melatonin Young Adult Pharmacokinetics Renal Dialysis Sleep Disorders Circadian Rhythm tasimelteon Internal medicine medicine Humans Pharmacology (medical) Renal Insufficiency Circadian rhythm Receptor Melatonin receptor agonist Dialysis Aged Benzofurans business.industry Liver Diseases Middle Aged United States Special Populations Tasimelteon Endocrinology Area Under Curve Female renal function impairment business pharmacokinetics dual melatonin receptor agonists Half-Life medicine.drug |
| Zdroj: | Journal of Clinical Pharmacology |
| ISSN: | 1552-4604 0091-2700 |
| DOI: | 10.1002/jcph.440 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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