We studied the effects of the commonly used -opioid receptor agonists morphine, oxycodone, methadone and the enantiomers of methadone in thermal and mechanical models of acute pain and in the spinal nerve ligation model of neuropathic pain in rats. Subcutaneous administration of morphine, oxycodone, and methadone produced a dose-dependent antinociceptive effect in the tail flick, hotplate, and ...

Methadone maintenance treatment (MMT) is the major tapering therapy for morphine addictive patients. There have gender differences reported in response to MMT. This study discovered that the estrogen-response element single nucleotide polymorphism (ERE-SNP; rs16974799, C/T) of cytochrome 2B6 gene (cyp2b6; methadone catabolic enzyme) responded differently to MMT dosing. Oestradiol was associated...

The outstanding properties of methadone are its analgesic activity, its efficacy by oral route, its extended duration of action in suppressing of withdrawal symptoms in physically dependent individuals, and its tendency to show persistent effects with repeated administration. The analgesic activity of methadone, a racemate, is almost entirely the result of its R-methadone content. Respiratory d...

BACKGROUND Despite evidence of the effectiveness of injectable opioid treatment compared with oral methadone for chronic heroin addiction, the additional cost of injectable treatment is considerable, and cost-effectiveness uncertain. AIMS To compare the cost-effectiveness of supervised injectable heroin and injectable methadone with optimised oral methadone for chronic refractory heroin addic...

Treatment of rats with desipramine (DMI) 1 hour before the subcutaneous administration of methadone increased the intensity and prolonged the duration of methadone analgesia, as determined by the hot plate method. DMI significantly reduced the analgesic ED50 of methadone from a control value of 3.4 to 1.6 or 0.5 mg/kg in rats treated with 20 or 30 mg/kg of DMI, respectively. DMI treatment also ...

Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of R- and S-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative sub...

To clarify the oxidative metabolism of methadone (R)- and (S)-enantiomers, the depletion of parent (R)- and (S)-methadone and the formation of racemic 2-ethylidene-1,5-dimethyl-3,3-diphe-nylpyrolidine were studied using human liver microsomes and recombinant cytochrome P450 enzymes. Based on studies with isoform-selective chemical inhibitors and expressed enzymes, CYP3A4 was the predominant enz...

INTRODUCTION Methadone, the most widely delivered maintenance therapy for heroin addicts, may be responsible for life-threatening poisonings with respiratory depression. The toxicokinetics and the toxicokinetic/toxicodynamic (TK/TD) relationships of methadone enantiomers have been poorly investigated in acute poisonings. The aim of this study was to describe the relationships between methadone-...

The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability. Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), catalyzed predominantly by CYP2B6. Retrospective studies suggest that the common allele variant CYP2B6*6 may influence methadone plasma concentrations. The catal...

The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability. Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1,5-dimethyl3,3-diphenylpyrrolidine (EDDP), catalyzed predominantly by CYP2B6. Retrospective studies suggest that the common allele variant CYP2B6*6 may influence methadone plasma concentrations. The cataly...