title: "Influence of methadone on clopidogrel in addicts on methadone maintenance therapy" Drug interaction between methadone and clopidogrel.
abstract: BACKGROUND
  Clopidogrel is a prodrug that converts in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. It seems that methadone as CYP2C19 inhibitor affects ticlopidine activity in vivo. This study aimed to test the ability of methadone in changing ticlopidine pharmacokinetics.
  
  
  METHODS
  We conducted a case-control study in 10 subjects. The cases (5 subjects) in our study were addicts who were receiving methadone maintenance treatment (MMT) for preventing opium withdrawal symptoms. The control group were opiate users before starting MMT. In both groups, the patients received clopidogrel (75mg/day) for 5 days. On the 6(th) day, the subjects returned to the clinic, blood samples were taken up to 12 hours following clopidogrel dosing in case and control groups. Plasma concentration of clopidogrel was measured by GC-MAS. Noncompartmental pharmacokinetic analysis was performed using Microsoft Excel software to estimate PK parameters.
  
  
  RESULTS
  In this study, methadone decreased clopidogrel clearance by 25% and increased the AUC0-inf nearly 1.3 fold during the coadministration of clopidogrel as an antiplatelet drug.
  
  
  CONCLUSIONS
  A significant decrease in the clearance of clopidogrel during the coadministration of methadone consistent with a decrease in clopidogrel conversion to its active metabolite and this may decrease its efficacy and may have life-threatening consequences for the patients undergoing clopidogerel maintenance therapy.
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Ferigol
authors.initials: F
authors.lastname: Fallah
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Abolhasan
authors.initials: A
authors.lastname: Hamidikenari
authors.affiliation: Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Seyed Navid
authors.initials: SN
authors.lastname: Sajadi
authors.affiliation: Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Seyed Rohollah
authors.initials: SR
authors.lastname: Sajadi
authors.affiliation: Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Shiran
keywords: Clopidogrel; Interaction; Methadone