Pharmacokinetics in children.

The first year of life is associated with major changes in the processes affecting the absorption, distribution, metabolism and excretion of drugs. Drug absorption by the oral route is affected by reduced gastric emptying so that this route is unreliable in the neonate. The intramuscular route is also unreliable but transdermal absorption is often greater, with risks of toxicity. The volume of distribution of many drugs is often markedly increased in the neonate, partly because of reduced plasma protein binding (both to albumin and to alpha-1-acid glycoprotein) but also because of an increased volume of extracellular fluid relative to total body water. These factors both result in increased half-life of elimination of drugs. Metabolic processes are often immature at birth and this results in reduced clearance rates and prolonged half-life of elimination of those drugs for which metabolism is a significant mechanism for elimination. Renal excretion in the newborn is reduced although glomerular filtration rate (a passive process) and active tubular secretory rate increase relatively rapidly during infancy. Since these processes tend to be the most important drug elimination mechanism for antibiotics, dose adjustment is particularly important; methods using calculated glomerular filtration rate and the role of therapeutic drug monitoring are described. Finally, the pharmacokinetic processes develop at different rates during the first year of life and an understanding of these factors can help in the safe and effective prescribing of antibiotics.