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Cited by 36Pain Management and Opioid UsePharmacogenetics and Drug MetabolismNeuropeptides and Animal Physiology

Single- and multiple-dose pharmacokinetics of samidorphan, a novel opioid antagonist, in healthy volunteers

Turncliff, Ryan, DiPetrillo, Lauren, Silverman, Bernard, Ehrich, Elliot·2015·Clinical Therapeutics
DOI 10.1016/j.clinthera.2014.10.001
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Abstract

Purpose 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.Methods 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.Findings 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.Implications In these single- and multiple-dose studies in healthy volunteers, samidorphan exhibited a pharmacokinetic profile consistent with once-daily dosing. ClinicalTrials.gov identifier: NCT00800319.

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Authors
Turncliff, R., DiPetrillo, L., Silverman, B., & Ehrich, E.
Affiliations
Alkermes (United States) (US)
ORCID
Silverman, Bernard
Venue
Clinical Therapeutics
Publisher
Elsevier BV
Published
2015-02
Volume
37
Issue
2
Pages
338-348
ISSN
0149-2918 (ISSN-L)
DOI
10.1016/j.clinthera.2014.10.001
OpenAlex
W2013358247
Cited by
36
References
15
Citations by year
2026: 1 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 8 · 2017: 1 · 2016: 1 · 2015: 2
FWCI
1.82
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Clinical Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
samidorphan, opioid antagonists, pharmacokinetics, oral administration, steady state, once-daily dosing, sleepiness, drug safety and tolerability, healthy volunteers
MeSH terms
Administration, Oral, Adult, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Half-Life, Humans, Male, Middle Aged, Morphinans, Naltrexone, Narcotic Antagonists, Area Under Curve, Dyssomnias, Healthy Volunteers

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