HCV Influences the Methadone Maintenance Treatment for Addiction

• Main Authors: Wu,Shiow-Ling, 吳秀玲
• Other Authors: Liu, Yu-Li
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/99395206054992693437

博士 === 國防醫學院 === 生命科學研究所 === 102 === Background and Objectives: Heroin-dependent patients typically contract hepatitis C virus (HCV) at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT) is a major treatment regimen for opioid dependence. HCV infection may affect methadone metabolism but this has rarely been studied. In our current study, we first established a method to measure the plasma concentrations of methadone and its metabolites under no enantiomer standard circumstances. We then aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan. Methods: A liquid chromatography-photodiode array (LC-PDA) method using a chiral analytical column was developed to determine the plasma levels of enantiomers of methadone and its chiral metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenyl pyrrolidine (EDDP), without the standard compounds of R-form or S-form enantiomers. This method was established by the characteristics of recombinant cytochrome P-450 (CYP) isozymes; where CYP2C19 prefers to metabolize R-methadone and CYP2B6 prefers to metabolize S-methadone. A total of 366 MMT patients were recruited and measured their plasma methadone and metabolite concentration. The levels of plasma hepatitis B virus (HBV), HCV, human immunodeficiency virus (HIV) antibodies (Ab), liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were measured along with the urine morphine concentration and amphetamine screening. Results: We incubated the racemic methadone standard with either enzyme for 24 hours. We identified the retention times of R- and S-methadone to be around 10.72 and 14.46 min, respectively. Of the 352 subjects in our cohort with HCV test records, 95% were found to be positive for plasma anti-HCV antibody. The liver functional parameters of AST (Wilcoxon Rank-Sum test, P=0.02) and ALT (Wilcoxon Rank-Sum test, P=0.04), the plasma methadone concentrations (Wilcoxon Rank-Sum test, P=0.043) and the R-enantiomer of methadone concentrations (Wilcoxon Rank-Sum test, P=0.032) were significantly higher in the HCV antibody-positive subjects than in the HCV antibody-negative patients, but not the S-EDDP/ methadone dose ratio. The HCV levels correlated with the methadone dose ( = 14.65 and 14.13; P=0.029 and 0.03) and the S-EDDP/ methadone dose ratio ( = -0.41 and -0.40; P=0.00084 and 0.002) in both univariate and multivariate regression analyses. Conclusions: We conclude that HCV may influence the methadone dose and plasma S-EDDP/ methadone dose ratio in MMT patients in this preliminary study.