Disposition of methadone in man after a single oral dose

The levels of methadone in the plasma and urine of 5 subjects giaven a single oral dose of 15 mg. have been determined using solvent extraction and gas‐liquid chromatography. Methadone was detected in plasma 30 minutes after drug administration. The peak plasma level occurred at 4 hours and was followed by an exponential decline during the next 20 hours. The mean apparent half‐life of methadone was 15 hours. The time action of methadone‐induced pupillary constriction closely coincided with the time course of methadone in plasma. An average of 52 per cent of the dose was excreted in the urine as methadone and metabolites in the 96 hours after drug administration. Nearly one half of the methadone and metabolites recovered in the urine was excreted during the first 24 hours. The renal clearance of methadone indicates that the drug is partially reabsorbed by a pH‐dependent process. These results demonstrate the importance of biotransformation and renal excretion as determinants of the disposition of methadone in man.