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Pharmacokinetics of Long‐Acting Naltrexone in Subjects With Mild to Moderate Hepatic Impairment
Author(s) -
Turncliff Ryan Z.,
Dunbar Joi L.,
Dong Qunming,
Silverman Bernard L.,
Ehrich Elliot W.,
Dilzer Stacy C.,
Lasseter Kenneth C.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005280199
Subject(s) - naltrexone , pharmacokinetics , medicine , anesthesia , pharmacology , opioid , receptor
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 (AUC 0‐∞ ) 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.