Methadone Pharmacokinetics:- A synthetic opioid with high oral: parenteral activity and its firm binding to tissue proteins. In single doses it is only slightly more potent than morphine and has comparable duration of action (4-6 hours on i.m. injection), but it cumulates in tissues on repeated administration--duration of action is progressively lengthened due to gradual release from these sites; plasma t 1/2 on chronic use is 24-36 hours. Plasma protein binding is 90% and it is metabolized in liver, primarily by demethylation and cyclization. Metabolites are excreted in urine. Uses:- Methadone has been used primarily as substitution therapy for opioid dependence: 1 mg of oral methadone can be substituted for 4 mg of morphine, 2 mg of heroin and 20 mg of pethidine. Another technique is methadone maintenance therapy in opioid addicts-- sufficient dose of methadone (10-40 mg/day) is given orally over long term to produce high degree of tolerance so that pleasurable effects of i.v. doses of morphine or heroin are not perceived and the subject gives up the habit. Ref:- kd tripathi; pg num:-476