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...

Methadone is widely used for the treatment of opioid dependence. Although in most countries the drug is administered as a racemic mixture of (R)- and (S)- methadone, (R)-methadone accounts for most, if not all, of the opioid effects. Methadone can be detected in the blood 15-45 minutes after oral administration, with peak plasma concentration at 2.5-4 hours. Methadone has a mean bioavailability...

BACKGROUND Methadone maintenance therapy (MMT) is a mainstay for treating opioid use disorder and preventing and managing HIV among people who inject drugs (PWID). While previous research suggested low dosing of methadone and high rates of discontinuation of MMT among PWID in Thailand, little is known about patients' lived experiences with MMT in this setting. Therefore, we conducted a mixed-me...

AIM To quantify gender, age-group and quantity of methadone prescribed as risk factors for drugs-related deaths (DRDs), and for methadone-specific DRDs, in Scotland's methadone-prescription clients. DESIGN Linkage to death-records for Scotland's methadone-clients with one or more Community Health Index (CHI)-identified methadone prescriptions during July 2009 to June 2013. SETTING Scotland'...

OBJECTIVE To investigate the pharmacokinetics (PK) and PK- pharmacodynamic (PD) relationship of methadone in a cohort of outpatients undergoing methadone maintenance treatment (MMT). METHODS Sixty male patients undergoing MMT with a mean ±SD methadone daily dosage of 58 ± 34 mg were enrolled in this study. A 5-ml blood sample was collected before the daily intake of methadone. As a PD measure...