Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants

Background: Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants. Methods: Perioperatively, 17 neonates and infants less than or equal to 160 days of age received one rectal paracetamol dose (mean 23.9 mg/kg (+/-4.2 mg/kg)). Blood samples were drawn at 60, 120, 180, 240, 300 and 360 min, according to the infants' weights. Plasma paracetamol concentrations were measured by a Colorometric Assay, Ectachem Clinical Chemistry Slides (Johnson & Johnson Clinical Diagsnostics). Results: The plasma paracetamol concentrations were mainly below the therapeutic (i.e, antipyretic) range of 66-132 mu mol/l and did not exceed 160 mu mol/l in any infant. The mean maximum plasma concentration (C(max)) was 72.4 mu mol/l (+/-33.5 mu mol/l) and the time to C(max), i.e. the mean T(max) was 102.4 min (+/-59.1 min). The mean "apparent" terminal half-life (n = 10) was 243.6 min (+/-114.1 min). Conclusion: The absorption of rectal paracetamol (mean dose 23.9 mg/kg, +/-4.2 mg/kg) in young infants <160 days is variable and often prolonged and achieves mainly subtherapeutic plasma concentrations.