STEREOSELECTIVE DISPOSITION OF METHADONE IN MAN

Stable isotope labeled methadone (pentadeuteromethadone) has been used in conjunction with gas chromatography-chemical ionization mass spectrometry to study plasma disappearance rates and urinary excretion of pharmacologically active R-(-)-methadone (l-methadone) and inactive S-(+)-methadone (d-methadone) in three adult methadone maintenance patients. In all three cases, the analgesically active enantiomeric form of the drug had a significantly longer elimination half-life (t 1 2β) when studied in a steady state than did the inactive form (t 1 2β for active R-(-)-methadone, 51.7 to 61.8 hours; t 1 2β for inactive S-(+)-methadone, 31.8 to 37.0 hours). The ratio of drug elimination half-lives } R-(-)-/S-(+)- ranged between 1.40 and 1.94. In the two cases so studied, slower plasma disappearance of active R-(-)-enatiomer than the inactive S-(+)-enantiomer was also observed (t 1 2β R-(-)-, 42.8 and 52.5 hours; t 1 2β S-(+)-, 38.3 and 41.3 hours). © 1979.