Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Acetaminophen Plasma Clearance Association With Race/Ethnicity
研究概览
简要总结
Although acetaminophen is the most commonly used nonprescription drug in the USA, little is known regarding the influence of genes and race/ethnicity on acetaminophen disposition. The investigators long-term goal is to understand the causes of differences in acetaminophen disposition between people that are the result of genetic variation and ethnicity and may predispose individuals to a higher risk of acetaminophen hepatotoxicity. The aim of this particular study is to measure the rate of elimination of acetaminophen via the 3 main pathways (glucuronidation, sulfation and oxidation) in self-identified White-Americans (n=100) and African-Americans (n=100). These rates will then be correlated with selected genetic polymorphisms in genes encoding enzymes involved in acetaminophen metabolism. Two main hypotheses will be tested: 1. African-Americans eliminate acetaminophen more rapidly by glucuronidation than do White-Americans. 2. Elimination via glucuronidation, sulfation, and oxidation in subjects will be significantly correlated with the presence of polymorphisms in the UGT1A6, SULT1A1, and CYP2E1 genes, respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •self-declared white/Caucasian
- •self-declared African-American
- •ambulatory
- •no evidence of medical disease
排除标准
- •alcohol use of 3 or more drinks per day
- •HIV or hepatitis (B or C) infection
- •isoniazid
- •disulfiram
- •phenobarbital
- •phenytoin
- •carbamazepine
- •rifampicin
- •valproic acid
- •probenecid
- •St. John's Wort
研究组 & 干预措施
White subjects
2 x 500 mg acetaminophen by mouth once
干预措施: Acetaminophen (Drug)
Black subjects
2 x 500 mg acetaminophen by mouth once
干预措施: Acetaminophen (Drug)
结局指标
主要结局
Acetaminophen Plasma Clearance Association With Race/Ethnicity
时间窗: 2 days
Plasma total clearance of acetaminophen in plasma measured by HPLC
Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity
时间窗: 2 days
Acetaminophen glucuronidation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity
时间窗: 2 days
Acetaminophen sulfation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity
时间窗: 2 days
Acetaminophen oxidation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Plasma Clearance Association With UGT2B15 Genotype
时间窗: 2 days
The association of UGT2B15 genotype with acetaminophen total clearance
Acetaminophen Glucuronidation Partial Clearance Association With UGT2B15 Genotype
时间窗: 2 days
The association of acetaminophen glucuronidation partial clearance with UGT2B15 genotype
APAP Plasma Adduct Association With UGT2B15 Genotype
时间窗: 2 days
The association of UGT2B15 genotype with APAP plasma adduct concentrations
次要结局
未报告次要终点