Children differ from adults in their response to drugs. Choice of dose is very important as there are huge variations in weight across the age range of birth to eighteen years, and also large changes in physical development, which affect drug distribution, excretion and metabolism. The most dramatic changes occur in the first year of life.

What pharmacokinetic changes occur in paediatric patients?

Absorption

Gastric emptying time is longer than adults up to about 6 months of age. Overall bioavailability (the proportion of a dose reaching the circulation) generally remains the same, but rate of absorption is slower and therefore onset of action may be delayed in neonates. Increased topical absorption may be seen in neonates and infants, due to the stratum corneum being thinner. As the body surface area to weight ratio is higher in this age group there is a greater potential for adverse effects. You should generally avoid giving intramuscular injections in paediatric patients. The lack of muscle mass means that injection is very painful, and the variability in blood flow means that absorption into the systemic circulation can be unpredictable.

Distribution

Important changes in body fat/water composition occur in the first year. Fat content rises from 12% to 30% from term to 1 year, while body water drops from 75% to 60%. For water soluble drugs, (e.g. gentamicin) larger doses on a mg/kg basis are required in a neonate compared to an older child in order to achieve therapeutic levels.

Metabolism

The liver is not fully developed until 6-12 months of age, hence drug metabolism is generally reduced in neonates. From years 1-5 however metabolic activity is increased compared to adults, and larger doses of metabolically cleared drugs (e.g. theophylline) may be required compared to adults on a mg/kg basis.

Dosing frequency in neonates

Look up the dose of chloramphenicol in the children’s BNF. How does the dosing regimen compare for:

- a neonate up to 14 days

- a neonate between 14-28 days

- a child >28 days old

What are the risks of chloramphenicol toxicity in a newborn?