Effect of maturation on drug disposition in pediatric patients.
Maturational changes in the physiologic processes that govern drug disposition in pediatric patients are described, and evaluation of data from pediatric drug studies is discussed. Gastrointestinal absorption depends on gastric pH, gastric emptying time, intestinal transit time, and gastrointestinal enzymatic activity; the overall effect of age-related alterations in these variables is poorly understood. Maturational changes in the skin affect percutaneous absorption. Distribution of drugs is affected by alterations in vascular perfusion, body composition, tissue binding, and plasma protein binding. For most water-soluble drugs, volume of distribution is increased in neonates. Age-related changes in biotransformation are complex because the rate of development of phase 1 and phase 2 metabolic pathways varies and metabolic pathways may be induced by in utero exposure to inducing agents. For most drugs, biotransformation is decreased in the neonate, increases from one to five years of age, and decreases after puberty to adult values. The kidneys of neonates are inefficient at drug elimination, leading initially to prolonged elimination half-lives of many drugs. Clearance of some drugs may be greater in infants than in older children and adults because of disproportionate development of renal filtration and secretion in relation to reabsorption. Few data on maturational changes in physiologic processes that affect drug disposition are available for any one drug in a specific pediatric population. In the development of research protocols, careful attention should be paid to the design limitations of published studies.
Stewart
C F
CF
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163.
Hampton
E M
EM
D000367:Age Factors; D000375:Aging; D001798:Blood Proteins / Q000378:metabolism; D001823:Body Composition; D002648:Child; D002675:Child, Preschool; D004790:Enzyme Induction; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D010599:Pharmacokinetics
D001798:Blood Proteins