Levo-Alpha-Acetylmethadol [KLH]

Understanding the drug interactions between antiretrovirals and opioid therapies may decrease toxicities and enhance adherence with improved HIV outcomes in opioid-dependent individuals. The authors report the results of a clinical pharmacology study designed to determine whether significant pharmacokinetic and/or pharmacodynamic interactions occur between the non-nucleoside reverse transcriptase inhibitor, delavirdine (DLV), and either methadone or levo-alpha acetyl methadol (LAAM) (n = 40). DLV significantly decreased methadone clearance (p=.018) and increased the methadone elimination half-life ( p <.001) with a resultant increase in AUC of 19% and C(min)of 29%. The combined effect of DLV on the total concentration of LAAM and its active metabolites, norLAAM and dinorLAAM, was to significantly increase AUC by 43% (p <.001), C-max by 30% (p <.013), and C-min by 59% (p <.004) while decreasing T-max (p <.05). Cognitive deficits over the seven-day study period as measured by the Mini-Mental State Examination, opioid withdrawal symptoms as measured by the Objective Opioid Withdrawal Scale, or complaints of adverse symptoms were not observed. Methadone and LAAM did not affect DLV concentrations. The findings from this study show that DLV treatment in methadone- or LAAM-maintained individuals results in altered opioid pharmacokinetics with an increased exposure and potential risk for opioid toxicity with methadone or LAAM treatment and an increased risk of cardiac toxicity with concomitant LAAM and DLV administration.

Aims Despite their potential advantages, many of the pharmacological interventions available to treat substance misuse are controversial and their acceptability within the United Kingdom (and other countries) has only recently begun to be investigated. Design A questionnaire mailed to British National Health Service (NHS) alcohol and drug treatment services asked respondents to rate the acceptability and availability of 11 pharmacological interventions for substance misuse employed to relieve withdrawal, reduce the likelihood of relapse and opiate overdose and substitute pharmaceuticals for illicit drugs. Participants A sample of NHS substance misuse services (n = 265) listed in one or more directories of services in England, Wales and Scotland. Findings Substitute methadone for opiate addiction, substitute benzodiazepines for benzodiazepine-dependent patients, lofexidine for opiate detoxification, naltrexone for opiate relapse prevention and acamprosate for alcohol relapse prevention were widely acceptable and available interventions. Another subset of medications-buprenorphine for opiate detoxification, take-home naloxone for overdose prevention and substitute prescribing of levo-alpha-acetyl-methadol (LAAM), heroin and dexamphetamine-garnered less support. but the majority of participants rated even these therapies as acceptable. Ultra-rapid detoxification under sedation was the intervention rated as least acceptable to, and was one of the two least frequently available from, responding NHS services. Conclusions Differences among specific medications notwithstanding, a wide range of harm-reduction and abstinence-orientated interventions were acceptable to and available from NHS services. Acceptance and availability are probably limited by a combination of practical, economic, safety, efficacy and theoretical considerations.