Single- and multiple-dose pharmacokinetics of samidorphan, a novel opioid antagonist, in healthy volunteers
| Autor: | Ryan Turncliff, Elliot Ehrich, Bernard L. Silverman, Lauren DiPetrillo |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.drug_class Samidorphan Narcotic Antagonists Administration Oral Pharmacology Naltrexone Drug Administration Schedule chemistry.chemical_compound Pharmacokinetics Double-Blind Method Opioid receptor Medicine Humans Pharmacology (medical) Dosing Dose-Response Relationship Drug business.industry Antagonist Middle Aged Dyssomnias Healthy Volunteers Tolerability chemistry Morphinans Area Under Curve Female business Opioid antagonist medicine.drug Half-Life |
| Zdroj: | Clinical therapeutics. 37(2) |
| ISSN: | 1879-114X |
| Popis: | Samidorphan (3-carboxamido-4-hydroxy naltrexone) is a novel opioid receptor antagonist that is currently in clinical development. The oral dose pharmacokinetics, safety, and tolerability of samidorphan were evaluated in 2 double-blind, placebo-controlled, randomized studies in healthy adults.The first study investigated single, ascending doses of 3.7 to 55.7 mg of samidorphan in 16 healthy adults; the second study evaluated multiple ascending doses of 10 or 20 mg of samidorphan administered for 7 days in 30 healthy adults.Across the two studies, 39 of 46 subjects were male; 32 were white, 11 were black, and 3 were hispanic. Mean age was 34.9 years and mean weight was 84.2 kg. In both studies, samidorphan was rapidly absorbed, with a Tmax of 1 hour, and AUC increased with increasing dose. Samidorphan plasma levels declined in a monoexponential manner, with a half-life of ~7 to 9 hours. After multiple doses, steady state was approached by day 6 and achieved by day 7 after the 10-mg dose, but steady state was not reached for the 20-mg dose. Accumulation was low, with accumulation ratios1.65. In both studies, samidorphan was generally well tolerated, with somnolence reported as the most common adverse event.In these single- and multiple-dose studies in healthy volunteers, samidorphan exhibited a pharmacokinetic profile consistent with once-daily dosing. ClinicalTrials.gov identifier: NCT00800319. |
| Databáze: | OpenAIRE |
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