Treatment with paracetamol in infants

Background: Paracetamol (N-acetyl-p-amino-phenol) or acetaminophen has beco me the most widely used analgesic and antipyretic in children. However, the re is a wide discrepancy between the extent to which paracetamol is used an d the Limited available pharmacological data in small infants. The purpose of this article is to present a review of the current Literature regarding the use of paracetamol in neonates and infants with a particular emphasis o n pharmacological issues. Methods: A MEDLINE search (up to March 2000) was conducted to identify rele vant English-language publications using paracetamol, children, infants and neonates as search terms. Additional studies were identified from bibliogr aphies of the reviewed literature. Results: Pharmacological studies on paracetamol in infants are few. Most st udies have focused on the administration of one single paracetamol dose, an d the problem of cumulative toxicity with repeated dosing has not been addr essed. Plasma paracetamol concentration should be 10-20 mg ml(-1) to achiev e antipyretic and analgesic effects. The bioavailability of the different f ormulations and routes of administration vary with age. Rectal absorption i s slower and more erratic than the oral; however, in the very young, rectal bioavailability is higher than in older patients. Volume of distribution s eems to be age-independent, whereas clearance is reduced in neonates and pa rticularly in preterm babies. Neonates and infants are capable of forming t he reactive intermediate metabolite that causes hepatocellular damage, part icularly after multiple doses. They have an immature glucuronide conjugatio n system, but the rate constant for the sulphation metabolic pathway is lar ger than in older children, and this is the most important route of metabol ism. Conclusions: The pharmacokinetics and pharmacodynamics of paracetamol diffe r substantially in neonates and infants from those in older children and ad ults; hence, dosing should be adjusted accordingly.