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Long-acting naltrexone is an extended-release formulation developed with the goal of continuous naltrexone exposure for 1 month for the treatment of alcohol dependence. The influence of mild and moderate hepatic impairment on naltrexone pharmacokinetics following long-acting naltrexone 190-mg administration was assessed. Subjects with mild (Child-Pugh grade A) and moderate (Child-Pugh grade B) hepatic impairment (n = 6 per group) and matched control subjects (n = 13) were enrolled. Naltrexone and 6β-naltrexol concentrations were determined over a period of 63 days following a single intramuscular dose. Naltrexone and 6β-naltrexol concentrations were detected in all subjects through 28 days. Total exposure (AUC0-∞) of naltrexone and 6β-naltrexol was similar across all groups. The long apparent half-lives of naltrexone and 6β-naltrexol (5–8 days) were attributed to the slow release of naltrexone (long-acting naltrexone exhibits absorption rate-limited elimination or “flip-flop” kinetics); elimination was not altered in subjects with hepatic impairment. Based on pharmacokinetic considerations, the dose of long-acting naltrexone does not need to be adjusted in patients with mild or moderate hepatic impairment.