Cotinine Metabolism in Infants and Children
| Status: | Archived |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | January 2007 |
| End Date: | June 2010 |
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.
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:
1. Determine the following in infants and children between 2 and 84 months of age dosed
with deuterium-labeled cotinine:
- The clearance of cotinine
- The half-life of cotinine
- The volume of distribution of cotinine
2. Validate the 3HC/Cot ratio in saliva and in urine as a marker of cotinine clearance and
half-life.
Secondary Specific Aims:
3. Determine the effects of age on the cotinine metabolite profile in the 8-hour urine
sample.
4. Determine if sulfation is a conjugation pathway for cotinine in infants and young
children.
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UCLA Medical Center Founded in 1955, UCLA Medical Center became Ronald Reagan UCLA Medical Center...
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