This proposal investigates the effect of diet on drug metabolism in the neonate by comparing the development of CYP450 enzyme activities between breast-fed and formula-fed infants The hypothesis tested by this proposal asserts that The development of cytochrome P450 1A and 2D functional activities is significantly different between breast-fed and formula-fed infants Specific experiments are designed to 1) Determine the relative activity of CYPIA2 between breast-fed and formula-fed infants being administered caffeine for the treatment of apnea, 2) Determine the relative activity of CYP1A2 and CYP2D6 between healthy breast-fed and formula-fed infants receiving subtherapeutic doses of caffeine and dextromethorphan, and 3) Determine the CYP2D6 genotype in infants participating in these studies to identify potential genotype-phenotype discordance for this polymorphically expressed enzyme Results will be obtained by measurement of caffeine serum half-life, assessment of CYP450 enzyme activity by measuring urinary drug metabolites and by the use of PCR-based techniques for genotyping assays The overall goals of this proposal are to determine the impact of infant diet on the activity of key drug metabolizing enzymes and to provide insight into the impact of ontogeny on their functional activity.
| Blake, Michael J; Abdel-Rahman, Susan M; Pearce, Robin E et al. (2006) Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants. Pediatr Res 60:717-23 |
| Blake, Michael J; Abdel-Rahman, Susan M; Jacobs, Richard F et al. (2006) Pharmacokinetics of rifapentine in children. Pediatr Infect Dis J 25:405-9 |
| Blake, Michael J; Castro, Lisa; Leeder, J Steven et al. (2005) Ontogeny of drug metabolizing enzymes in the neonate. Semin Fetal Neonatal Med 10:123-38 |
