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Cotinine Metabolism in Infants and Children

Institution: University of California, San Francisco
Investigator(s): Neal Benowitz, M.D.
Award Cycle: 2006 (Cycle 15) Grant #: 15RT-0229 Award: $509,473
Subject Area: Public Health, Public Policy, and Economics
Award Type: Research Project Awards

Initial Award Abstract
Second hand smoke is a general health hazard, but second hand smoke is particularly hazardous to children. Second hand smoke is a major cause of respiratory tract infection, middle ear infection, asthma, respiratory problems requiring hospitalization, and Sudden Infant Death Syndrome (SIDS). Infant passive smoking is the foremost modifiable risk factor for SIDS prevention. Epidemiology studies provide the basis for our understanding of the hazards of second hand smoke. Good epidemiology requires good dose exposure estimate. Cotinine is made from nicotine by the liver. Many epidemiology studies have used concentrations of cotinine in urine, blood or saliva to estimate second hand smoke exposure. Of note, cotinine levels are typically higher in children compared to adults exposed to second hand smoke, and often some infants and young children have levels consistent with active smoking. An important question is whether this represents much higher second hand smoke exposure, or whether children metabolize nicotine and/or cotinine differently from adults. This is a very important distinction from a public health perspective. To interpret cotinine levels in relation to nicotine exposure, one must understand the metabolism and elimination in individuals. Much research has been published (mostly from our laboratory) on the metabolism and kinetics of nicotine and cotinine in adults. We have also published a study of newborns. Virtually nothing is known about these issues in infants and children. There is reason to believe, based on other drugs, that nicotine and cotinine metabolism will change with age (comparing infants through early childhood). We propose novel research to characterize developmental changes in the metabolism of cotinine through early childhood. Seventy-two infants and children ages 2 months to 72 months will be given oral doses of cotinine. Urine and saliva samples will be collected for 10 days after the cotinine dose. From these data, we will calculate how fast cotinine is eliminated in infants and young children. Our results will be of directly utility in interpreting cotinine levels of children of different ages as biomarkers of second hand smoke exposure. In addition the general information to be gained on developmental changes in CYP2A6 enzyme activity (involved in the activation of a number of carcinogens, including some tobacco-specific nitrosamines) is relevant to understanding the impact of second hand smoke exposure in children to the development of cancer later in life.