Effect of Severe Alcoholic Liver Disease on the Disposition of Methadone in Maintenance Patients

We studied methadone disposition in 11 maintenance patients with alcoholic liver disease of such severity that liver biopsy was con‐traindicated. Nine methadone‐maintained patients with recent alcohol abuse but minimal or no evidence of liver disease served as controls. Most kinetic indices, including the apparent oral clearance and area under the concentration‐time curves, were similar in patients and controls. Although the apparent terminal half‐life of methadone was longer (p= 0.04) in the patients with liver disease, the peak plasma methadone level was lower (p= 0.03). None of the patients had signs or symptoms of methadone overdosage or abstinence at the time of study. Six patients and one control had flattened plasma methadone concentration‐time curves. We hypothesize that, in severe liver disease, damage to hepatic drug‐metabolizing systems is offset by damage to the capacity of the liver to store and release unchanged methadone. The usual methadone maintenance dose may be continued in stable patients with severe alcoholic cirrhosis.