Medication-Assisted Treatment of Opiate Dependence Is Gaining Favor.
Medication-assisted treatment of opiate dependence is gaining favor.
Cleve Clin J Med. 2013 Jun; 80(6): 345-9
Jerry JM, Collins GB
People addicted to opiates are more likely to avoid returning to these drugs if they participate in a program that includes taking maintenance doses of methadone or buprenorphine than with an abstinence program. Although medical opinion has long been divided on the issue of abstinence vs medication-assisted treatment, the latter seems to be gaining respect as an evidence-based approach.
HubMed – Methadone
Mechanism of Autoinduction of Methadone N-Demethylation in Human Hepatocytes.
Anesth Analg. 2013 Jun 3;
Campbell SD, Crafford A, Williamson BL, Kharasch ED
BACKGROUND:There is considerable interindividual and intraindividual variability in methadone metabolism and clearance. Methadone dosing is particularly challenging during initiation of therapy, because of time-dependent increases in hepatic clearance (autoinduction). Although methadone N-demethylation is catalyzed in vitro by cytochrome P4502B6 (CYP2B6) and CYP3A4, and clearance in vivo depends on CYP2B6, mechanism(s) of autoinduction are incompletely understood. In this investigation, we determined mechanism(s) of methadone autoinduction using human hepatocytes.METHODS:Fresh human hepatocytes were exposed to 0.1 to 10 µM methadone for 72 hours. Cells were washed and methadone N-demethylation assessed. CYP2B6, CYP3A4, and CYP3A5 messenger RNA (mRNA), protein expression (by gel-free high-performance liquid chromatography mass spectrometry) and catalytic activity (bupropion hydroxylation and alfentanil dealkylation for CYP2B6 and CYP3A4/5, respectively) were measured. Mechanisms of CYP induction were characterized using pregnane X receptor and constitutive androstane receptor reporter gene assays.RESULTS:Methadone (10 µM) increased methadone N-demethylation 2-fold, CYP2B6 and CYP3A4 mRNA 3-fold, and protein expression 2-fold. CYP3A5 mRNA was unchanged. CYP2B6 and CYP3A4/5 activities increased 2-fold. Induction by methadone enantiomers (R-methadone versus S-methadone) did not differ. Induction was relatively weak compared with maximum induction by phenobarbital and rifampin. Lower methadone concentrations had smaller effects. Methadone was an agonist for the pregnane X receptor but not the constitutive androstane receptor.CONCLUSIONS:Methadone caused concentration-dependent autoinduction of methadone N-demethylation in human hepatocytes, related to induction of CYP2B6 and CYP3A4 mRNA expression, protein expression, and catalytic activity. Induction was related to pregnane X receptor but not constitutive androstane receptor activation. These in vitro findings provide mechanistic insights into clinical autoinduction of methadone metabolism and clearance.
HubMed – Methadone
Medications for substance use disorders.
Soc Work Public Health. 2013 May; 28(3-4): 264-78
Douaihy AB, Kelly TM, Sullivan C
In this article, the authors briefly review the pharmacotherapeutic agents that are currently available for the treatment of substance use disorders. Nicotine replacement therapies are most effective for tobacco cessation. Naltrexone, acamprosate, and disulfiram are effective for reducing alcohol use. The most effective pharmacotherapies for opiate use disorders are agonist therapies, including methadone and buprenorphine. The authors also examine recent advances in medication development for other substance use disorders such as stimulant addiction. The role of medication adherence and behavioral treatments and the integration of behavioral and pharmacotherapeutic interventions are also discussed.
HubMed – Methadone
METHADONE – Methadone Madness Public outrage tonight as the city planner recommends approval of London’s sixth methadone clinic. Hundreds of residents turned out for a m…
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