Clinical trial NCT00994591: Cotinine Metabolism in Infants and Children
Official title: Cotinine Metabolism in Infants and Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Secondhand Smoke Exposure
Keywords: Nicotine
Cotinine
CYP2A6
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2009-10-14
Enrollment: 56
Sex: ALL
Minimum age (years): 2
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Ages: 12 months, 13-24 months, and 25-83 months
* Caucasian (including Hispanic) and African American only
* Some exposure to secondhand smoke

Exclusion Criteria:

* Any medical problems
* Taking prescription medication (there are exceptions)

Primary outcomes:
measure: Cotinine clearance
timeFrame: 8 hours
Secondary outcomes:
measure: Half-life of cotinine
timeFrame: 8 hour
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco, SFGH, CTSI,CRC
state: California
Study officials:
affiliation: University of California, San Francisco
name: Neal L Benowitz, MD
role: PRINCIPAL_INVESTIGATOR
References: