Stereoselective disposition of methadone in man.期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Stereoselective disposition of methadone in man.

Authors:	M J Kreek D L Hachey P D Klein

Affiliation:	1. The Rockefeller University 1230 York Avenue New York, New York 10021, USA;2. Section of Medical Development Division of Biological and Medical Research Argonne National Laboratory Argonne, Illinois 60439, USA

Abstract:	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 ( $t_{12β}$ ) when studied in a steady state than did the inactive form ( $t_{12β}$ for active R-(?)-methadone, 51.7 to 61.8 hours; $t_{12β}$ 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 ( $t_{12β}$ R-(?)-, 42.8 and 52.5 hours; $t_{12β}$ S-(+)-, 38.3 and 41.3 hours).

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