Metabolic interactions between opiates and alcohol.

1. Acute preperfusion with ethanol does not alter significantly the initial hepatic extraction or subcellular distribution of narcotics, or the immediate biotransformation of the long-acting narcotic, methadone, using the isolated perfused rabbit liver. However, the acute administration of ethanol may alter distribution and/or impair hepatic drug metabolism in perfusion studies of longer duration, or in vivo, as has been suggested by others in studies of several drugs. 2. Following chronic treatment with both ethanol and methadone in the rat, plasma levels of unmetabolized methadone, determined by gas liquid chromatography, are significantly lowered. 3. Following chronic treatment with methadone alone, blood elimination rates of ethanol are accelerated to a greater extent than following chronic treatment with ethanol alone in the rat; following chronic treatment with both methadone and ethanol, rates of ethanol elimination are accelerated to a significantly more rapid rate than following treatment with either agent alone. 4. To date, clinical studies in patients on chronic steady-dose methadone maintenance treatment, without liver disease, polydrug abuse, or heavy use of ethanol, show no significant acute dispositional interactions between methadone and ethanol. 5. Clinical studies in patients on chronic steady-dose methadone maintenance treatment, without liver disease, polydrug abuse, or heavy use of ethanol, show no significant dispositional interactions between methadone and disulfiram (Antabuse) when the latter was given for one week for study purposes only. 6. Clinical studies of possible dispositional interactions between methadone and ethanol in methadone-maintained patients, who are also chronic abusers of alcohol, are now in progress.