Initial and subsequent dosing of rectal acetaminophen in children

A 24-hour pharmacokinetic study of new dose recommendations

Patrick K Birmingham*, Michael J. Tobin, Dennis M. Fisher, Thomas K. Henthorn, Steven C Hall, Charles J. Coté

*Corresponding author for this work

Research output: Contribution to journalArticle

89 Citations (Scopus)

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 μg/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 rain 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 μg/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 μg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.

Original languageEnglish (US)
Pages (from-to)385-389
Number of pages5
JournalAnesthesiology
Volume94
Issue number3
DOIs
StatePublished - Jan 1 2001

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Acetaminophen
Pharmacokinetics
Serum
Antipyretics
Rain

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Birmingham, Patrick K ; Tobin, Michael J. ; Fisher, Dennis M. ; Henthorn, Thomas K. ; Hall, Steven C ; Coté, Charles J. / Initial and subsequent dosing of rectal acetaminophen in children : A 24-hour pharmacokinetic study of new dose recommendations. In: Anesthesiology. 2001 ; Vol. 94, No. 3. pp. 385-389.
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title = "Initial and subsequent dosing of rectal acetaminophen in children: A 24-hour pharmacokinetic study of new dose recommendations",
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 μg/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 rain 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 μg/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 μg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.",
author = "Birmingham, {Patrick K} and Tobin, {Michael J.} and Fisher, {Dennis M.} and Henthorn, {Thomas K.} and Hall, {Steven C} and Cot{\'e}, {Charles J.}",
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Initial and subsequent dosing of rectal acetaminophen in children : A 24-hour pharmacokinetic study of new dose recommendations. / Birmingham, Patrick K; Tobin, Michael J.; Fisher, Dennis M.; Henthorn, Thomas K.; Hall, Steven C; Coté, Charles J.

In: Anesthesiology, Vol. 94, No. 3, 01.01.2001, p. 385-389.

Research output: Contribution to journalArticle

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T1 - Initial and subsequent dosing of rectal acetaminophen in children

T2 - A 24-hour pharmacokinetic study of new dose recommendations

AU - Birmingham, Patrick K

AU - Tobin, Michael J.

AU - Fisher, Dennis M.

AU - Henthorn, Thomas K.

AU - Hall, Steven C

AU - Coté, Charles J.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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 μg/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 rain 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 μg/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 μg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.

AB - 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 μg/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 rain 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 μg/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 μg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.

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