Journal Article

Single- and Multiple-dose Pharmacokinetics of Samidorphan, A Novel Opioid Antagonist, in Healthy Volunteers

Turncliff, Ryan, Ehrich, Elliot, Silverman, Bernard, DiPetrillo, Lauren

2015

Overview

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 ratios <1.65. 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.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Administration, Oral / Adult / Area Under Curve / Dose-Response Relationship, Drug / Double-Blind Method / Drug Administration Schedule / Drug dosages / Drug therapy / Dyssomnias - chemically induced / Female / Half-Life / Healthy Volunteers / Humans / Internal Medicine / Male / Medical Education / Metabolism / Middle Aged / Morphinans - administration & dosage / Morphinans - adverse effects / Morphinans - pharmacokinetics / multiple ascending dose trial / Naltrexone - administration & dosage / Naltrexone - adverse effects / Naltrexone - analogs & derivatives / Naltrexone - pharmacokinetics / Narcotic Antagonists - administration & dosage / Narcotic Antagonists - adverse effects / Narcotic Antagonists - pharmacokinetics / opioid receptor antagonist / pharmacokinetics / safety / samidorphan / single ascending dose trial / Studies / tolerability