Population Pharmacokinetics: Methadone-Antiretroviral Interactions in Vietnam

人群药代动力学：越南美沙酮抗逆转录病毒药物的相互作用

• 批准号: 9274233
• 负责人: GAVIN BART
• 金额: $ 35.35万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274233
• 关键词: ABCB1 gene; AIDS prevention; Africa South of the Sahara; Anti-Retroviral Agents; Area; CYP2B6 gene; Caring; Clinical; Collection; Country; Data; Dose; Drug Interactions; Drug Kinetics; Drug Modelings; Drug Monitoring; Drug usage; Epidemic; Future; Genetic; Genetic Polymorphism; Genotype; Goals; HIV; HIV Infections; HIV risk; High Prevalence; Injection of therapeutic agent; Knowledge; Laboratories; Lead; Measures; Methadone; Modeling; Morbidity - disease rate; Nevirapine; Opiate Addiction; Opiates; Oral; Patient Care; Patients; Pharmaceutical Preparations; Pharmacogenetics; Pharmacology; Pharmacotherapy; Physicians; Population; Recommendation; Regimen; Research Personnel; Research Proposals; Risk Behaviors; Sample Size; Scientist; Substance Withdrawal Syndrome; Therapeutic Uses; Time; Translating; Vietnam; Viral hepatitis; Withdrawal; Withdrawal Symptom; Work; addiction; antiretroviral therapy; base; clinical decision-making; design; efavirenz; healthy volunteer; improved; injection drug use; innovation; methadone maintenance; non-nucleoside reverse transcriptase inhibitors; pharmacokinetic model; predictive modeling; public health relevance; response; support tools; therapy adherence; tool

 DESCRIPTION (provided by applicant): Approximately one in three new HIV infections occurring outside of sub-Saharan Africa is related to injection drug use. Because this epidemic is primarily driven by the injection of opiates, several countries have initiated methadone maintenance treatment as part of their HIV prevention, treatment, and care strategy. In many of these settings more than 30% of patients entering methadone treatment are HIV+. Most will be on antiretroviral therapies (ART) at some point during their treatment with methadone. Interactions between the two most commonly used ART in the world, nevirapine (NVP) and efavirenz (EFV), and methadone are well known but poorly characterized in clinical populations. These interactions frequently lead to opiate withdrawal symptoms, patient destabilization, and return to drug use that results in a cascade of poor ART adherence and increased morbidity related to drug use and inconsistent HIV care. Adjustment of methadone dose in the setting of methadone-ART interactions can return the patient to stability. There are no clear data to help a clinician determine the extent to which a methadone dose should be adjusted following methadone-ART interactions. Currently, clinicians must guess on methadone dose adjustments until the desired clinical response is achieved. The overall goal of our work is to The following research proposal focuses on the creation of a population pharmacokinetic model of methadone in a real-world clinical setting with a high prevalence of HIV and use of NVP and EFV. This will be accomplished through two specific aims: 1) Use population pharmacokinetics in a real-world clinical setting to measure differences in methadone exposure (e.g., area under the concentration-time curve, AUC; and relationship between dose and apparent oral clearance, CL/F) between those on NVP or EFV and those not on NVP or EFV, respectively; and 2) Evaluate the influence of selected genetic polymorphisms on methadone pharmacokinetics and methadone-NVP and -EFV interactions.

 描述（由申请人提供）：撒哈拉以南非洲地区以外发生的大约三分之一的新艾滋病毒感染与注射吸毒有关，因为这种流行病主要是由注射阿片类药物引起的，因此一些国家已启动美沙酮维持治疗作为其一部分。他们的艾滋病毒预防、治疗和护理策略 在许多此类环境中，超过 30% 的接受美沙酮治疗的患者为艾滋病毒阳性。美沙酮是世界上最常用的两种抗逆转录病毒治疗药物奈韦拉平 (NVP) 和依非韦伦 (EFV) 与美沙酮之间的相互作用，但在临床人群中却鲜为人知，这些相互作用经常导致阿片戒断症状、患者不稳定和复发。药物使用会导致 ART 依从性差、与药物使用相关的发病率增加以及不一致的 HIV 护理，在美沙酮与 ART 相互作用的情况下调整美沙酮剂量可能会恢复。目前，没有明确的数据可以帮助临床医生确定美沙酮与 ART 相互作用后应调整的程度，直到达到预期的临床反应为止。我们工作的目标是以下研究计划的重点是在艾滋病毒高流行和使用 NVP 和 EFV 的现实临床环境中创建美沙酮的群体药代动力学模型，这将通过两个具体目标来实现： 1）使用人口真实世界临床环境中的药代动力学，以测量服用 NVP 或 EFV 的人和未服用 NVP 或 EFV 的人之间美沙酮暴露的差异（例如，浓度-时间曲线下面积，AUC；以及剂量与表观口服清除率之间的关系，CL/F）分别为 NVP 或 EFV；以及 2) 评估选定的基因多态性对美沙酮药代动力学以及美沙酮-NVP 和-EFV 相互作用的影响。