Purpose of review: Toxicity concerns and awareness during anesthesia issues continue to concern pediatric anesthesiologists. Most developmental pharmacokinetic, pharmacodynamic and pharmacogenomic changes occur within the first year of life. Understanding these early changes can improve drug use in this cohort.
Recent findings: Growth and development are two major aspects of children not readily apparent in adults. Clearance in the pediatric population should be investigated using models that describe size, maturation and organ function influences. Glucuronide conjugation (hepatic phase II process) mirrors glomerular filtration maturation over the first year of life. Phase 1 processes appear more rapid, and differences attributable to single nuclear polymorphisms may be obvious by the end of the 4-week neonatal period in term infants.Pharmacodynamic differences in infancy remain poorly defined, and neonatal pharmacokinetic-pharmacodynamic analyses that might elucidate such differences are few, partly because of a paucity of effective pharmacodynamic measures.
Summary: Mechanistic models create a framework for the study of pharmacokinetic changes in infancy. Understanding these changes allows a target concentration approach to therapy and potential for reduced toxicity. The target concentration may be undefined because of a paucity of effect measures.