Evaluation of levo-alpha-acetylmethdol (LAAM) as an alternative treatment for methadone maintenance patients who regularly experience withdrawal: a pharmacokinetic and pharmacodynamic analysis
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- 作者：Newcombe ; David A.L. ; Bochner ; Felix ; White ; Jason M. ; Somogyi ; Andrew A.
- 关键词：Methadone ; LAAM ; Holders ; Non-holders ; Pharmacokinetics ; Pharmacodynamics
- 刊名：Drug and Alcohol Dependence
- 出版年：2004
- 出版时间：October 5, 2004
- 年：2004
- 卷：76
- 期：1
- 页码：63-72
- 全文大小：141 K
文摘
The aim of this study was to determine if substitution of daily methadone with second daily levo-alpha-acetylmethadol (LAAM) would convert non-holders on methadone into holders on LAAM, and to compare plasma concentration–time profiles of (R)-methadone with LAAM and its two metabolites. Sixteen stable methadone maintenance treatment participants (non-holders, n=8) were randomly allocated to continue methadone for 3 months or switch to LAAM for 3 months, and then crossed over to the alternative drug for 3 months. At steady state, there were two testing sessions (24h for methadone and 48h for LAAM), during which opioid withdrawal severity, respiration rate and pupil diameter were measured 10–11 times and venous blood was collected 13–15 times. Ten age- and gender-matched controls underwent one 48-h test session. Areas under the withdrawal severity score versus time curve (AUC0–47 hours for LAAM and controls; AUC0–24 × 2 for methadone) were similar in holders on methadone and LAAM (P=0.62), but were greater in non-holders when they were taking methadone than LAAM (P<0.001). Respiratory depression and pupillary constriction were similar for LAAM and methadone. In comparison to (R)-methadone, plasma nor- and dinor-LAAM concentrations fluctuated little over the dosing interval. LAAM converted methadone non-holders into LAAM holders. LAAM may therefore be useful in selected MMT non-holders and improve retention in opioid treatment programs.