Treatment with paracetamol in infants

BACKGROUND: Paracetamol (N-acetyl-p-amino-phenol) or acetaminophen has become the most widely used analgesic and antipyretic in children. However, there is a wide discrepancy between the extent to which paracetamol is used and 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 on pharmacological issues. METHODS: A MEDLINE search (up to March 2000) was conducted to identify relevant English-language publications using paracetamol, children, infants and neonates as search terms. Additional studies were identified from bibliographies of the reviewed literature. RESULTS: Pharmacological studies on paracetamol in infants are few. Most studies have focused on the administration of one single paracetamol dose, and the problem of cumulative toxicity with repeated dosing has not been addressed. Plasma paracetamol concentration should be 10-20 mg ml(-1) to achieve antipyretic and analgesic effects. The bioavailability of the different formulations and routes of administration vary with age. Rectal absorption is slower and more erratic than the oral; however, in the very young, rectal bioavailability is higher than in older patients. Volume of distribution seems to be age-independent, whereas clearance is reduced in neonates and particularly in preterm babies. Neonates and infants are capable of forming the reactive intermediate metabolite that causes hepatocellular damage, particularly after multiple doses. They have an immature glucuronide conjugation system, but the rate constant for the sulphation metabolic pathway is larger than in older children, and this is the most important route of metabolism. CONCLUSIONS: The pharmacokinetics and pharmacodynamics of paracetamol differ substantially in neonates and infants from those in older children and adults; hence, dosing should be adjusted accordingly.