Table 2.

Summary of pharmacokinetic differences in paediatric populations compared with adults

	Developmental change	PK consequence	Drugs affected	Examples
Absorption	↓Intestinal transit	↓Cmax and ↓AUC	Poorly solubles	Theophylline
			Sustained release formulations
	↓Gastric pH	↑Cmax for weak acids	Weak acids	Penicillin
	↓Cmax for weak bases	Weak bases	Itraconazole
	↓Intestinal bile concentration	↓Cmax and ↓AUC	Poorly solubles	Hydrocortisone
Distribution	Body composition	↔Vd (neonates have relatively reduced fat whereas infants have relatively increased fat compared with adults; extracellular water is relatively higher in neonates compared with preschool children)	Lipophilic drugs ↓Vd in neonates and ↑Vd in infants compared with adults Hydrophilic drugs ↑Vd in infants compared with neonates	Diazepam Aminoglycosides (e.g. gentamycin)
	↓plasma protein	↑free fraction of drug in plasma ↑Vd	Highly protein bound drugs	Phenytoin, salicylates, ampicillin, nafcillin, sulfisoxazole and sulfamethoxyphrazine
Metabolism	Larger relative size of liver	↑hepatic clearance of drugs	Those extensively metabolized	Theophylline, caffeine, carbamazepine and valproic acid
	Ontogeny of liver enzymes	↔hepatic metabolism of drugs	Drugs metabolism by specific pathways eg UDP glucuronosyl transferase	Chloramphenicol
	Bacterial colonization of the intestine	↑Cmax and ↑AUC	Those metabolized within the gut	Digoxin
Elimination	Larger relative size of kidney	↑renal clearance in infants and preschool children	Those excreted unchanged in urine	Levetiracetam, cimetidine and certirizine
	Ontogeny of tubular transporters	↔renal clearance of drugs	Those susceptible to tubular transport	Digoxin