Cotinine Metabolism in Infants and Children
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Cotinine clearance
研究概览
简要总结
Levels of cotinine, a biomarker for nicotine, have been found to be higher in infants and small children than adults. This pharmacokinetic study is designed to determine whether children metabolize cotinine differently than adults.
Seventy-two healthy children between the ages of 2 months and 6 years will come with their mothers to SFGH GCRC for one approximately 9 hour visit. After being examined by a pediatrician, the child will be administered one dose of cotinine at .05 mg/kg.
Saliva and urine samples will be collected prior to dosing and throughout the day to characterize the metabolism and excretion of cotinine. The investigators have previously shown that a ratio of 3'-hydroxycotinine/cotinine (3HC/Cot) in saliva correlates closely to nicotine metabolism.
Following these one day hospital visits, a research assistant will visit the participants in their homes to collect urine and saliva samples at 1,2,3,7, and 10 days after the initial dose.
详细描述
The long-term goal is to characterize developmental changes in CYP2A6 activity and nicotine and cotinine metabolism in infants and children. Our hypotheses are:
- The rate of nicotine and cotinine metabolism and the level of CYP2A6 activity will increase with age throughout infancy and childhood.
- The rate of cotinine glucuronidation (reflecting UGT 1A4 and 1A9 activity) will increase with age.
- Cotinine clearance will be lower and cotinine half-life longer in African-Americans compared to Caucasians.
- The excretion of cotinine glucuronide will be less among African-Americans compared to Caucasians.
- Developmental increases in CYP2A6 will be greatest in children with wild type CYP2A6 genes, and will be lower in children who have CYP2A6 gene variants associated with reduced activity.
This present study is the first step in the investigation of the above hypotheses. The primary goal of this study is to determine if there are age-related changes in cotinine clearance and validate the 3HC/COT ratio as a biomarker of cotinine clearance and half-life. This biomarker can then be used in larger studies to explore the hypotheses described above. The biomarker could also be used in epidemiologic studies of the health effects of SHS in infants and children.
Primary Specific Aims:
- Determine the following in infants and children between 2 and 84 months of age dosed with deuterium-labeled cotinine:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 2 Months 至 72 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ages: 12 months, 13-24 months, and 25-83 months
- •Caucasian (including Hispanic) and African American only
- •Some exposure to secondhand smoke
排除标准
- •Any medical problems
- •Taking prescription medication (there are exceptions)
研究组 & 干预措施
Pharmacokinetic dosing
干预措施: Pharmacokinetic dosing (Drug)
结局指标
主要结局
Cotinine clearance
时间窗: 8 hours
次要结局
- Half-life of cotinine(8 hour)