STEREOSELECTIVE PHARMACOKINETICS OF METHADONE IN CHRONIC PAIN PATIENTS

Ten patients with chronic pain were randomized to an open, balanced, c rossover study. Each patient received two different preparations of ra cemic methadone, i.e., tablets and intravenous infusion. The pharmacok inetic parameters of the R- and S-enantiomers of the racemate are repo rted. The analgesically active R-methadone has a significantly longer mean elimination half-life than the optical antipode S-methadone (t1/2 = 37.5 and 28.6 h, respectively). The mean total volume of distributi on is 496.6 L for R-methadone and 289.1 L for S-methadone. Significant differences in the mean clearance between R- and S-methadone are seen (0.158 and 0.129 L/min, respectively). However, the lagtime after ora l administration and the bioavailability did not show differences betw een the isomers. The data suggest that both enantiomers of methadone s hould be measured if correlations between pharmacodynamics and kinetic s are made due to the stereoselective differences in half-life, total volume of distribution, and clearance.