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                            Library & Multimedia
 Metabolic and toxicological considerations of the opioid replacement therapy and analgesic drugs: methadone and buprenorphine
NCJ Number
              307078

Author(s)
          D. E. Moody
Date Published

2013
Length
              23 pages
Annotation
              The author of this article addresses and examines various options for treatment of opioid dependence through a literature review of peer-reviewed publications on PubMed, including articles cited.
Abstract
              Methadone and buprenorphine are maintenance replacement therapies for opioid dependence; they are also used for pain management. Methadone and buprenorphine (to a lesser extent) have seen sharp increases in mortality associated with their use. They have distinct routes of metabolism (mostly cytochrome P450 dependent), and distinct pharmacologic activity of metabolites. As such, metabolism may play a role in differences in their toxicity. This article reviews peer-reviewed literature obtained from PubMed searches and literature referenced within. The review considers first an overview of drug use and mortality over the past decade. It then provides extensive detail on the*in vitro*and*in vivo*human metabolism of methadone and buprenorphine. Using both human and experimental animal studies it then presents the pharmacodynamic activity of parent drug and metabolites at the mu-opioid receptor, as P-glycoprotein substrates and plasma/brain concentration ratios, and activity at the hERG K+ channel. Lessons learned from drug interaction studies in humans are then examined in an attempt to bring together the combined information. The use and misuse of these drugs contributes to the epidemic in opioid-associated mortalities. A better understanding of metabolism-, transport- and co-medication-induced changes will contribute to their safer use. (Publisher Abstract Provided)
      
  
          Additional Details
Grant Number(s)
        2011-DN-BX-K532


  
  
        
  Agencies
        NIJ-Sponsored


  
  
        
  Publication Type
        Research (Applied/Empirical)


  
  
        
  Award
        Prediction of drug interactions with methadone, buprenorphine and oxycodone from in vitro inhibition of metabolism
    
  
  
Date Published: January 1, 2013
    
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