Levo-Alpha-Acetylmethadol [BSA]

Methadone is a full -opioid receptor agonist used in the treatment of heroin addiction. It is commercialized as a racemic mixture with considerable variability in the pharmacokinetics and pharmacodynamics between individuals that can affect dose-response and toxicological profile. This review aims to discuss metabolomics of methadone, namely by presenting all major and minor metabolites and pharmacokinetic drug interactions. The main mechanism for methadone metabolism is hepatic through the cytochrome P450, specifically isoenzymes 2B6, 3A4 and 2D6. Firstly, methadone is N-demethylated and cyclize to form its major 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyraline (EMDP) metabolites. Several alternate minor pathways have been described namely various methadol metabolites, which proved to be active.It is expected that knowing the metabolomics of methadone may provide further insights, attempting a personalized therapy aiming to attain effective blood concentrations. The historical record is therefore especially important when investigating clinical and forensic cases related to methadone administration, since interindividual responses are known to vary considerably.

Background: Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose. Methods: After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sub-lingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3X/week urine toxicology tests, and weekly self-reported illicit drug use. Results: There were no significant differences at baseline in important social, demographic and drug-use features. Retention was 71% in the daily and 77% in the 3X/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3X/week, There were no significant differences between groups in self-reported number of bags of heroin wed for any day of the week, including Thursdays (48-72 hours following the last buprenarphine dose for subjects in the 3X/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%), Conclusions: At art equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug Else. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings. (C) 2000 Society of Biological Psychiatry.