The 131st Annual Meeting (November 15-19, 2003) of APHA

Abstract #70852

Gary Ginsberg, PhD, Connecticut Department of Public Health, P.O. Box 340308 Mail Stop 11CHA, Hartford, CT 06134, 860-509-8000, gary.ginsberg@po.state.ct.us, Bob Sonawane, PhD, National Center for Environmental Assessment/ Office of Research and Development, United States Environmental Protection Agency, 1200 Pennsylvania Ave, NW Mail Code 8623D, Washington, DC 20460, and Dale Hattis, PhD, The George Perkins Marsh Institute, Clark University, 950 Main St, Worcester, MA 01610-1477.

There are many physiologic features that are unique to infants. These factors cause the pharmacokinetics of drugs (absorption, distribution, metabolism, excretion) to be different in infants than in adults. To evaluate these differences, a database was developed for 45 therapeutic drugs whose pharmacokinetics have been studied both in children and adults. Overall, neonates in the first week of life were 2-4 fold slower than adults in drug clearance, with this differential decreasing with advancing maturity. Of particular note is the slower clearance of caffeine in neonates as compared to its close structural analogue, theophylline. PBPK modeling results indicate that the major metabolic route for both drugs in adults (CYP1A2) is approximately 100 times slower in neonates. However, theophylline has additional metabolic pathways that are not available to caffeine. These pathways are minor or non-existant in adults but become predominant in neonates. This raises important questions about how environmental toxicants are likely to be handled in neonates.

Child/adult differences are also likely in terms of susceptibility to carcinogens. A review of animal cancer studies indicates greater sensitivity to a single dose of carcinogen given in early life than when the same dose was given to mature animals. This is consistently seen with mutagens and likely stems from the much greater cell division rates in early life. This enhanced sensitivity may also apply to young children, but classical risk assessment methods do not capture this factor. However, newer approaches are beginning to take into account children's unique pharmacokinetics and carcinogen susceptibility.

Learning Objectives:

At the conclusion of the session, the participant (learner) will be able to:
• convey the importance of pharmacokinetics in governing internal dose and risk;
• understand how children's unique physiology and functional immaturities can alter chemical absorption, metabolism, and excretion relative to adults;
• understand how these pharmacokinetic differences may affect children's risks from environmental toxicants;
• understand that children are likely to be at greater risk to carcinogens, especially those that are mutagens, than adults;
• convey how cancer risk assessment is traditionally conducted and how this obscures child/adult differences in pharmacokinetics and susceptibility; and
• understand newer approaches which more fully take into account the factors which govern childen's risks.

Keywords: Children's Health, Environmental Health

Presenting author's disclosure statement:
I do not have any significant financial interest/arrangement or affiliation with any organization/institution whose products or services are being discussed in this session.