Initial and Subsequent Dosing of Rectal Acetaminophen in Children

Author:

Birmingham, AF1-0567 Patrick K.1,Tobin Michael J.1,Fisher Dennis M.2,Henthorn Thomas K.3,Hall Steven C.4,Coté Charles J.5

Affiliation:

1. Assistant Professor of Anesthesiology.

2. Professor of Anesthesia and Pediatrics, University of California, San Francisco. Current position: Medical Director, Durect Corporation, Cupertino, California.

3. Professor of Anesthesiology and Chair, University of Colorado.

4. Professor of Anesthesiology and Chair.

5. Professor of Anesthesiology and Pediatrics, Northwestern University at Children’s Memorial Hospital.

Abstract

Background Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 microg/ml, without evidence of accumulation. Methods Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration. Results All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 microg/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses. Conclusions A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10-20 microg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Reference16 articles.

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