Cotinine Metabolism in Infants and Children (1058)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00994591
Recruitment Status : Completed
First Posted : October 14, 2009
Last Update Posted : May 24, 2013
Information provided by (Responsible Party):
University of California, San Francisco

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.

Condition or disease Intervention/treatment Phase
Secondhand Smoke Exposure Drug: Pharmacokinetic dosing Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Cotinine Metabolism in Infants and Children
Study Start Date : January 2007
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Arm Intervention/treatment
Experimental: Pharmacokinetic dosing Drug: Pharmacokinetic dosing
Pharmacokinetic testing involves dosing with deuterated cotinine which has an associated IND#61329.

Primary Outcome Measures :
  1. Cotinine clearance [ Time Frame: 8 hours ]

Secondary Outcome Measures :
  1. Half-life of cotinine [ Time Frame: 8 hour ]

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Ages Eligible for Study:   2 Months to 72 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00994591

United States, California
University of California, San Francisco, SFGH, CTSI,CRC
San Francisco, California, United States, 94101
Sponsors and Collaborators
University of California, San Francisco
Principal Investigator: Neal L Benowitz, MD University of California, San Francisco

Responsible Party: University of California, San Francisco Identifier: NCT00994591     History of Changes
Other Study ID Numbers: 10-03693
First Posted: October 14, 2009    Key Record Dates
Last Update Posted: May 24, 2013
Last Verified: May 2013

Keywords provided by University of California, San Francisco: