Chapter 23 - Drug Therapy in Neonates and Pediatric Patients

Abstract

This chapter discusses drug therapy in neonates and pediatric patients. The use of drugs in newborns, infants, and children is often based on safety, efficacy, and pharmacological data generated in adults. The practice of scaling adult drug doses to infants and children based on body weight or body surface area (BSA) does not account for the developmental changes that affect drug pharmacokinetics (PK) or target tissue and organ sensitivity to the drug. The ratio of absorptive surface area to BSA is greater in infants and children than in adults. Although pancreatic enzyme excretion is low in newborns, malabsorption does not occur and no effect on drug absorption has been observed. The newborn intestine is colonized with bacteria within days of birth, but the spectrum of bacterial flora may change over the first few years of life. The capacity of the liver to metabolize drugs is lower at birth, and the rate of development of various metabolic pathways is highly variable and may be influenced by exposure to drugs in utero and postnatally. The administration of cisapride to premature infants for the treatment of gastroesophageal reflux illustrates the clinical relevance of the ontogeny of cytochrome P450 3A4 (CYP3A4). Clinical experience shows that dosing according to BSA usually results in more uniform plasma drug concentrations across a broad age range.