Genetic Polymorphism Analysis == Genomic DNA was extracted from venous blood samples using a FlexiGene DNA kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions

Genetic Polymorphism Analysis == Genomic DNA was extracted from venous blood samples using a FlexiGene DNA kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions. better outcome of the MMTP. == 1. Introduction == Methadone maintenance treatment programs (MMTPs) have been shown to be effective in reducing illicit drug use and risks Top1 inhibitor 1 of human immunodeficiency virus (HIV) and hepatitis C (HCV) contamination [13]. Achievement of an optimal methadone plasma concentration is crucial for a successful MMTP [4]. However, due to wide interindividual variations in methadone pharmacokinetics [57], some patients’ methadone plasma concentrations may be too difficult to reach within a therapeutic range even though they receive higher dosages. Between 30% and 80% of patients are considered poor responders to MMTPs [8], and 98.6% of injecting drug users (IDUs) on a MMTP still continue to inject drugs [9]. Some factors are thought to influence the methadone plasma concentration and treatment responses. IDUs may have severe medical complications of material use disorders, including psychiatric disease (e.g., depressive disorder, stress) [1012], infectious diseases (HIV, HCV) Top1 inhibitor 1 [13], and pain disorders [14]. In addition, many treatment conditions can result in complications. For example, methadone-drug interactions (MDIs) could occur because MMTP clients have a high tendency Top1 inhibitor 1 towards taking concomitant medications (72%) [15]. Approximately 48% of patients have at least one MDI, and the most common MDI is usually benzodiazepines (38.1%), such as alprazolam and estazolam. Moreover, methadone interactions with some antiretroviral brokers are also ubiquitous in HIV-MMTP clients [16,17]. Some antiretroviral brokers are well-documented as cytochrome P450 (CYP450) 3A4, 2B6, or 2D6 strong inducers (e.g., efavirenz) [18] or inhibitors. In a case report [19], interruption in the use of lopinavir-ritonavir brought on Torsade de Pointes (TdP) by increasing the methadone plasma concentration, because lopinavir-ritonavir may induce metabolic clearance of methadone involving CYP3A4, 2B6, and 2D6 enzymes. Observational andin vitrostudies have suggested thatCYP2B6[2023],2C19[21,22], andABCB1[22,24] genetic polymorphisms have important roles in gene codes for methadone-metabolizing enzymes and transporter proteins (p-glycoprotein, P-gp). CYP2B6 has been demonstrated to be an important contributor to S-methadone metabolism, and CYP2C19 preferentially metabolizes R-methadone [21,25]. S-methadone has been found to contribute to higher levels of dissatisfaction and the risk of QT interval prolongation [26,27]. R-methadone has been reported to be associated with clinical effects as a result of its stronger activation of-opioid receptors [28]. Methadone is usually a substrate of P-gp, encoded by the multidrug resistance1 (ABCB1) gene, which has the ability to influence the bioavailability Top1 inhibitor 1 of orally administered methadone in the gastrointestinal tract and hepatocytes and has an effect on mediating methadone transport through the blood-brain barrier (BBB) [29,30]. Even though joint genetic effects of CYP and P-gp on a MMTP have been demonstrated in some pharmacogenetic studies [20,3134], few studies have simultaneously considered other important factors, such as disease says, MDIs, and poly-substance use, in assessing the methadone treatment responses, particularly in the ethnic Chinese populations. It is especially important that medical professionals understand the efficacy of and crucial factors related to MMTPs. In Taiwan, to encounter the escalating IDUs and HIV infections through needle sharing, the first MMTPs were implemented in July 2006 [35,36]. However, a thorough evaluation on the treatment responses of a MMTP has not yet been conducted. Therefore, the main purpose of this pilot study was to simultaneously evaluate the influence of genetic variations ofCYP2B6,CYP2C19, andABCB1,disease says, MDIs, and poly-substance use around the methadone steady-state trough plasma level and treatment responses in MMTP patients. In addition, as the methadone plasma dose and plasma concentration may be severely interfered by antiretroviral drugs, we recruited non-HIV patients to avoid the impact of antiretroviral brokers around the MMTP and to evaluate the potential factors related to the methadone plasma concentration and treatment responses more precisely. == 2. Materials and Methods == == 2.1. Study Patients == This study was conducted from February 2010 to December 2011 at Jianan Mental Hospital of the Department of Health, the first mental hospital to implement a MMTP, and Chung-Ho Memorial Hospital of Kaohsiung Medical University, a major medical center in southern Taiwan. One hundred and seventy-eight patients with no HIV contamination (confirmed by medical records) aged 20 years and who were not pregnant were recruited. To ensure that patients’ methadone plasma concentrations Top1 inhibitor 1 were at the steady-state condition and have stable methadone doses, patients who had participated in the MMTP 1 month were recruited. == 2.2. Ethics Statement == All information was kept strictly confidential and used for research proposes only. The study was approved by the Institutional GFPT1 Review Boards of Jianan Mental Hospital (Approval number.