Drug Disposition in the Pediatric Patient

Abstract

The pediatric patient is a unique individual who undergoes continual physiologic change from the time of conception through adolescence. The pharmacokinetics of therapeutic agents are influenced by physiologic changes that ultimately affect drug therapy. The gastric absorption of many therapeutic agents is altered by changes in gastric pH, gastric emptying, intestinal motility, biliary function, pancreatic function, and regional blood flow. Intramuscular absorption is erratic and unpredictable because of reduced skeletal muscle mass, alterations in regional blood flow, and physical activity. Percutaneous absorption is increased in the neonate due to increased water content and decreased thickness of the stratum corneum. The distribution of many therapeutic agents is increased in the neonate and infant because of an increase in extracellular fluid and total body water, alterations in tissue binding, and decreased plasma protein binding. The metabolic capacity and elimination processes of the newborn are greatly reduced compared to the adult; hepatic function is approximately one-half that of adults and renal elimination is similarly reduced. Hepatic function in the infant and young child may actually exceed that in the adult due to the increase in hepatic metabolic surface area to body weight ratio. Renal function matures relatively quickly in the neonate and approaches adult drug renal elimination rates within the first year of life. There is a lack of clinical research that defines therapeutic guidelines in the pediatric patient for specific drugs. However, an understanding of these physiologic changes that take place during growth and development in the pediatric patient will facilitate optimal drug therapy in this patient population. Following the initiation of drug therapy, the continued physiologic changes taking place in the pediatric patient necessitate continual therapeutic drug monitoring and periodic dosage adjustments. These special considerations challenge and enhance the responsibility of the pharmacist as a key member in assuming safe and effective pediatric drug therapy.