24-HOUR PHARMACOKINETICS OF RECTAL ACETAMINOPHEN IN CHILDREN - AN OLDDRUG WITH NEW RECOMMENDATIONS

Background: Rectal acetaminophen is often administered during operatio n to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampli ng times. The authors extended the drug sampling period to more clearl y define acetaminophen pharmacokinetics in children having surgery. Me thods: Children (n = 28) were randomized to receive a single dose of 1 0, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia, Venous blood samples were taken every 30 min for 4 h, every 60 min fo r 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effect s modeling technique (using NONMEM software) to determine the volume o f distribution and clearance normalized for bioavailability. Additiona l models accounted for suppository dissolution followed by acetaminoph en absorption. Results: Age, weight, estimated blood loss, volume of i ntravenous fluid administered, and anesthesia time were similar in the three groups, Most patients did not achieve peak or sustained serum v alues in the 10-20 mu g/ml serum concentration range associated with a ntipyresis. The volume of distribution was 385 ml/kg, and clearance no rmalized fur bioavailability, F, was 5.46 ml.kg(-1).min(-1). Pharmacok inetic models suggest that absorption of acetaminophen is a function o f zero-order dissolution of suppositories and first-order absorption f rom the rectum. Suppository dose size also may affect absorption chara cteristics. Conclusions: The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the ant ipyretic serum concentration of 10-20 mu g/ml. Based on the observed k inetics, the authors recommend that the initial dose should be approxi mately 40 mg/kg.