Footnotes Competing Interests: The authors have declared that no competing interests exist. Funding: This study was supported by grants from the Wellcome Trust (Programme Grant reference number is 082809/Z/07/Z) (to P.M.S.) Medical Research Council G84/6638 (to A.A.). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation selleck inhibitor of the manuscript.
Methadone is a synthetic opioid that is generally used as a replacement therapy to counteract withdrawal symptoms in heroin-dependent patients [1]. Higher incidence rates of hepatitis C virus (HCV) infection have been reported in these patients who are under methadone treatment [2], [3]. Epidemics of blood borne infectious diseases in heroin-injecting users has aroused worldwide public health concerns with HCV infection emerging as one of the most serious problems among these epidemics [4].

Compared with a prevalence of 0.3 to 14.5% in the general population, HCV infection has an incidence of 50% to 95% among drug needle users [5]�C[7]. Patients infected with HCV experienced a series of hepatic tissue damages including acute hepatitis, chronic inflammation, fibrosis and cirrhosis [8]. Furthermore, the risk of hepatocellular carcinoma is extraordinarily high among these individuals [9]. As the liver is the key metabolic organ, it is critical to evaluate the extent to which HCV infection would influence its metabolic functions. This knowledge will assist clinicians to adjust the medications when treating affected patients. Methadone contains a chiral center that allows the compound to produce R-form and S-form enantiomers [10].

Methadone is extensively metabolized in the liver through specific isoforms of the cytochrome P-450 enzyme system [11]. It has been reported that methadone is metabolized by CYP2B6, CYP2C19, CYP3A4 and, to a lesser extent, by CYP2D6 [11]�C[13]. The CYP isozymes have preferential metabolic differences between the methadone enantiomers, with CYP2C19 preferring to metabolize the R-form and CYP2B6 the S-form [11]. The effects of HCV on methadone metabolism remain poorly Brefeldin_A understood; it has been reported however that cirrhosis and late-stage liver failure may interfere with methadone metabolism [14]. MMT patients may require high methadone dosages to maintain an adequate blood concentration [14]. In our present study, we hypothesized that the HCV serostatus would determine the methadone metabolic profiles by influencing CYP2B6 genetic function. First, we examined the association of the HCV serostatus with the methadone metabolic profiles from a cohort of MMT patients. We then examined the impact of the HCV serostatus on CYP2B6 gene expression.