en pharmacology pharmacology Original Article Original Article <p dir="ltr" style="text-align: justify;"><span style="font-family: times new roman;"><span style="color: rgb(0, 0, 255);"><strong><em>Background: </em></strong></span>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 i<em>n vivo</em>. This study aimed to test the ability of methadone in changing ticlopidine pharmacokinetics.</span></p> <p dir="ltr" style="text-align: justify;"><span style="font-family: times new roman;"><span style="color: rgb(0, 0, 255);"><strong><em>Methods:</em></strong></span> We conducted a case&ndash;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.&nbsp; 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&nbsp; control groups. Plasma concentration of clopidogrel was measured by GC-MAS. Noncompartmental pharmacokinetic analysis was performed using Microsoft Excel software to estimate PK parameters.</span></p> <p dir="ltr" style="text-align: justify;"><span style="font-family: times new roman;"><span style="color: rgb(0, 0, 255);"><strong><em>Results:</em></strong></span> In this study, methadone decreased clopidogrel clearance by 25% and increased the AUC_0-inf nearly 1.3 fold during the coadministration of clopidogrel as an antiplatelet drug.</span></p> <p dir="ltr" style="text-align: justify;"><span style="font-family: times new roman;"><span style="color: rgb(0, 0, 255);"><strong><em>Conclusion:</em></strong></span> 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</span></p> Clopidogrel, Methadone, Interaction 133 135 http://caspjim.com/browse.php?a_code=A-10-256-1&slc_lang=en&sid=1 Ferigol Fallah 10031947532846005290 10031947532846005290 No Psychiatry and Behavioral Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran Abolhasan Hamidikenari 10031947532846005291 10031947532846005291 No Psychiatry and Behavioral Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran Seyed Navid Sajadi 10031947532846005292 10031947532846005292 No Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran Seyed Rohollah Sajadi 10031947532846005293 10031947532846005293 No . Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Reza Shiran mr.shiran@gmail.com 10031947532846005294 10031947532846005294 Yes Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran