Further complications are that little data is available concerning the disposition of drugs in infants before the general release of new drugs. Also studies in infants and young children are difficult to perform because of the limited amount of sample which can be collected. The most dramatic changes occur in the first year, thereafter dose adjustments can be made on a weight or surface area basis without too many problems. The bioavailability of acid labile penicillins is increased in newborns. Delayed gastric emptying and irregular intestinal peristalsis leads to slower absorption of some drugs in infants and young children.
Extravascular fluid is proportionately higher at earlier age as well.
In general distribution volumes expressed as volume per body weight tend to be larger in neonates than in adults and decrease towards adult values during childhood. This has been observed for ampicillin, ticarcillin, and amikacin. Binding to plasma proteins appears to be less in newborn infants compared with older children and adults. This appears to be true for both acidic and basic drugs. The presence of competing substances, such as bilirubin in premature infants, complicates the picture.