4 - Determinants of drug disposition in infants

Abstract

This chapter discusses the pharmacokinetics and determinants of drug disposition in infants. Drug exposure of infants by transmission from breast milk is a common clinical reality. The effects of drug exposure depend not only on the dose ingested in milk but also on its distribution and elimination in the infant. The issue may be approached by considering the individual pharmacodynamic factors that determine the steady state concentration of a drug in plasma—namely; bioavailability, a measure of the fraction of oral dose that reaches the systemic circulation; the dose; the rate constant for elimination; the apparent volume of distribution; and the dosing interval. The infant's response depends not only on the pharmacodynamic properties of the drug but also on the disposition of the drug in the infant. Adverse reactions to a drug may be due to its slow elimination from the body as well as tissue sensitivity. When excretion is retarded, a drug may accumulate to toxic amounts despite ingestion of a small quantity in milk. Physiological maturation with increasing age has a significant influence on drug bioavailability and distribution and on hepatic and renal clearance, which are important determinants of steady state drug concentrations in plasma. In addition, the type of drug, for example, whether it is metabolized or excreted directly in the kidneys, must be taken into account in the assessment of the consequences of drug intake via the breast milk.