Role of CYP2B6 Polymorphisms in Methadone Metabolism and Clearance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Methadone Metabolism
研究概览
简要总结
This research study will determine if genetic variation in CYP2B6 affects how the body metabolizes methadone.
详细描述
This investigation determined the influence of CYP2B6 genetic variation, specifically CYP2B6*6 polymorphism, on clinical methadone plasma concentrations, clearance, and metabolism. The hypothesis was that CYP2B6*6 heterozygotes or homozygotes would have reduced metabolism and clearance. A secondary objective was to evaluate other less common genotypic variants, when encountered. Healthy volunteers in genotype cohorts CYP2B6*1/*1, CYP2B6*1/*6 , and CYP2B6*6/*6, and also CYP2B6*4 and CYP2B6*5 carriers, received single doses of IV and oral methadone. Plasma and urine methadone and metabolite concentrations were determined by tandem mass spectrometry. The primary outcome measure was methadone metabolism, measured as plasma metabolite/patent area under the concentration-time curve ratio and metabolite formation clearance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Each subject must meet all of the following criteria:
- •18-50 yr old
- •CYP2B6*1/*1, CYP2B6*1/*6 or CYP2B6*6/*6 genotype
- •Good general health with no remarkable medical conditions
- •BMI < 33
- •Provided informed consent
排除标准
- •Subjects will not be enrolled if any of the following criteria exist:
- •Known history of liver or kidney disease
- •Use of prescription or non prescription medications, herbals or foods known to be metabolized by or affect CYP2B6
- •Females who are pregnant or nursing
- •Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction)
- •Direct physical access to and routine handling of addicting drugs in the regular course of duty (this is a routine exclusion from studies of drugs with addiction potential)
研究组 & 干预措施
Methadone arm
- Intravenous racemic methadone HCl, 6.0 mg bolus
- Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)
干预措施: IV racemic methadone HCl (Drug)
Methadone arm
- Intravenous racemic methadone HCl, 6.0 mg bolus
- Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)
干预措施: Oral racemic methadone HCl (Drug)
结局指标
主要结局
Methadone Metabolism
时间窗: up to 96 hours
Plasma metabolite EDDP/methadone area under the concentration-time curve (AUC0-96) ratio
次要结局
未报告次要终点