Brain and plasma levels of methadone and their relationships to analgesic activity of methadone in rats.

The levels of methadone in brain and plasma of rats after acute administration of several different doses of methadone were measured at several time points and relationships to analgesic activity were examined. Both brain and plasma levels of methadone as well as the analgesic activity of methadone, expressed as analgesic area and as percentage of maximum possible effect, were all increased by increasing dosage. All these measurements dropped rapidly after reaching the peak levels 30 min after administration of methadone. At the time of maximal analgesia, the analgesic effect of methadone was quantitatively related to both brain and plasma levels of methadone with 50% of the analgesic maximum possible effect corresponding to the concentrations of 1.44 nmol/g and 0.52 nmol/ml of methadone in brain and plasma, respectively. Our data suggest that measurement of changes in the plasma concentration of methadone at the time of maximal analgesia reflects changes in the brain concentration of methadone and may provide an index of changes in the analgesic effect of methadone.