Pharmacokinetics of rectal paracetamol after major surgery in children

Abstract

Glycogelatin capsular suppositories containing a paracetamol slurry 40 mg.kg-1 were given PR to 20 children (12 months-17 yrs) after major orthopaedic surgery and plasma concentrations of paracetamol measured for up to 18 h. The mean maximum concentration (Cmax) was 0.115 (SD 0.049) mmol.l-1. Peak concentration occurred (Tmax) at 2.3 (SD 1.2) h. Mean concentration was 0.07 (SD 0.03) mmol.l-1 at six h. Apparent paracetamol clearance was 5.8 ml.min-1.kg-1. The plasma concentration of paracetamol associated with analgesic effectiveness in children is unknown, but antipyretic effects are seen in the range 0.066-0.130 mmol.l-1. Paracetamol suppositories 40 mg.kg-1 given perioperatively achieve effective therapeutic antipyretic plasma concentrations within 1-2 h. The timing is coincident with the recovery phase of short duration paediatric surgery. The coefficient of variance of Cmax was 43%. Some individual patients may not achieve a Cmax which is therapeutic.