Phase I study of injectable, depot naltrexone for the relapse prevention treatment of opioid dependence

• Published in: The American journal on addictions Vol. 23; no. 2; pp. 162 - 169
• Main Authors: Xuyi, Wang, Juelu, Wang, Xiaojun, Xiang, Haiyan, Li, Zheyuan, Liu, Zhehui, Gong, Guoming, Dong, Gang, Liu, Jin, Li, Wei, Hao
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2014
• Subjects: Adult; Concentration; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - adverse effects; Dosage; Double-Blind Method; Drug dependency; Female; Humans; Injections; Male; Naltrexone; Naltrexone - administration & dosage; Naltrexone - adverse effects; Naltrexone - blood; Naltrexone - pharmacokinetics; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - adverse effects; Narcotic Antagonists - blood; Opioid-Related Disorders - prevention & control; Prevention; Safety; Secondary Prevention; Young Adult
• ISSN: 1055-0496; 1521-0391
• DOI: 10.1111/j.1521-0391.2013.12085.x

Background and Objectives We tested long‐acting injectable depot naltrexone for its tolerability, pharmacokinetics, and safety in Phase I. Methods The Phase I trial enrolled 36 healthy participants in two panels (A, B). In Panel A, 24 subjects were randomly assigned to the high‐dosage group (400 mg naltrexone, n = 6; placebo, n = 6) or low‐dosage group (200 mg naltrexone, n = 6; placebo, n = 6). In Panel B, 12 subjects were randomized to take six doses of monthly injectable naltrexone (400 mg) or placebo. Results After a single injection of naltrexone 200 and 400 mg, means (SD) of naltrexone plasma concentrations were .57 (.28) ng/ml and 1.5 (.8) ng/ml 30 days post‐injection. There was no effect of accumulation after multiple dosing. Eleven of 30 subjects (36.67%) who were administered injectable depot naltrexone reported a total of 12 adverse events (AEs). Seven of these 11 AEs were coded as possibly related with study medication. All treatment‐related AEs were mild in severity. No serious treatment‐related AEs occurred. Discussion and Conclusions This long‐acting formulation of injectable depot naltrexone is well tolerated, results in constant plasma concentration of naltrexone for at least 1 month. Scientific Significance The tolerability and safety of long‐acting injectable depot naltrexone are good. (Am J Addict 2014;23:162–169)