Abstract
Ten patients with chronic pain were randomized to an open, balanced, crossover study. Each patients received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported. 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 distribution 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 oral administration and the bioavailability did not show differences between the isomers. The data suggest that both enantiomers of methadone should be measured if correlations between pharmacodynamics and kinetics are made due to the stereoselective differences in half-life, total volume of distribution, and clearance.
| Original language | English |
|---|---|
| Journal | Therapeutic Drug Monitoring |
| Volume | 18 |
| Issue number | 3 |
| Pages (from-to) | 221-7 |
| Number of pages | 7 |
| ISSN | 0163-4356 |
| Publication status | Published - Jun 1996 |
Keywords
- Aged
- Analgesics, Opioid
- Biological Availability
- Chromatography, High Pressure Liquid
- Chronic Disease
- Cross-Over Studies
- Double-Blind Method
- Female
- Half-Life
- Humans
- Male
- Methadone
- Middle Aged
- Pain
- Pilot Projects
- Stereoisomerism