The neonate, infant and child32

Young human beings differ greatly from adults, not merely in size but also in the proportions and constituents of their bodies and the functioning of their physiological systems. These differences are reflected in the way the body handles and responds to drugs and are relevant to prescribing.

• Rectal absorption is efficient with an appropriate formulation and has been used for diazepam and theophyllines; this route may be preferred with an uncooperative infant.

• The intramuscular or subcutaneous routes tend to give unpredictable plasma concentrations, e.g. of digoxin or gentamicin, because of the relatively low proportion of skeletal muscle and fat. Intravenous administration is preferred in the seriously ill newborn.

31 Vessell E S 1982 Clinical Pharmacology and Therapeutics 31:1.

32 A neonate is under 1 month and an infant is 1-12 months of age.

• Drugs or other substances that come in contact with the skin are readily absorbed as the skin is well hydrated and the stratum corneum is thin; overdose toxicity may result, e.g. with hexachlorophane used in dusting powders and emulsions to prevent infection.

An understandable reluctance to test drugs extensively in children means that reliable information is often lacking. Many drugs do not have a licence to be used for children, and their prescription must be 'off licence', a practice that is recognised as necessary, if not actually promoted, by the UK drug regulatory authorities.

Distribution of drugs is influenced by the fact that total body water in the neonate amounts to 80% as compared to 65% in older children. Consequently:

• Weight-related priming doses of aminoglycosides, aminophylline, digoxin and frusemide need to be larger for neonates than for older children.

• Less extensive binding of drugs to plasma proteins is generally without clinical importance but there is a significant risk of elevation of plasma bilirubin (in the neonate) following its displacement from protein binding sites by vitamin K, x-ray contrast media or indomethacin.

Metabolism. Although the enzyme systems that inactivate drugs are present at birth, they are functionally immature, expecially in the preterm baby, and especially for oxidation and for conjugation with glucuronic acid. Inability to conjugate and thus inactivate chloramphenicol causes the fatal 'grey' syndrome in neonates. After the first weeks of life the drug metabolic capacity increases rapidly and young children may require a higher weight-related dose than adults because of their more rapid metabolic rates.

Elimination. Glomerular filtration, tubular secretion and reabsorption are low in the neonate (even lower in preterm babies) only reaching adult values in relation to body surface area at 2-5 months. Therefore drugs that are eliminated by the kidney (e.g. aminoglycosides, penicillins, diuretics) must be given in reduced dose; after about 6 months,

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