Twenty-four-hour pharmacokinetics of rectal acetaminophen in children

An old drug with new recommendations

Patrick K Birmingham*, Michael J. Tobin, Thomas K. Henthorn, Dennis M. Fisher, Maura C. Berkelhamer, Frederick A. Smith, Kaaren B. Fanta, Charles J. Coté

*Corresponding author for this work

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Background: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. Methods: Children (n = 28) were randomized to receive a single dose of 10, 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 for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. Results: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 μg/nd serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml · kg-1 · min-1. Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption from the rectum. Suppository dose size also may affect absorption characteristics. Conclusions: The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10-20 μg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.

Original languageEnglish (US)
Pages (from-to)244-252
Number of pages9
JournalAnesthesiology
Volume87
Issue number2
DOIs
StatePublished - Oct 22 1997
Externally publishedYes

Fingerprint

Acetaminophen
Pharmacokinetics
Suppositories
Pharmaceutical Preparations
Serum
Biological Availability
Anesthesia
Antipyretics
Blood Volume
Rectum
Analgesia
Software
Guidelines
Weights and Measures

Keywords

  • Analgesics: acetaminophen
  • Anesthesia: pediatric
  • Pharmacokinetics: modelling
  • Pharmacology: acetaminophen; rectal

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Birmingham, P. K., Tobin, M. J., Henthorn, T. K., Fisher, D. M., Berkelhamer, M. C., Smith, F. A., ... Coté, C. J. (1997). Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: An old drug with new recommendations. Anesthesiology, 87(2), 244-252. https://doi.org/10.1097/00000542-199708000-00010
Birmingham, Patrick K ; Tobin, Michael J. ; Henthorn, Thomas K. ; Fisher, Dennis M. ; Berkelhamer, Maura C. ; Smith, Frederick A. ; Fanta, Kaaren B. ; Coté, Charles J. / Twenty-four-hour pharmacokinetics of rectal acetaminophen in children : An old drug with new recommendations. In: Anesthesiology. 1997 ; Vol. 87, No. 2. pp. 244-252.
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abstract = "Background: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. Methods: Children (n = 28) were randomized to receive a single dose of 10, 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 for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. Results: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 μg/nd serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml · kg-1 · min-1. Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption from the rectum. Suppository dose size also may affect absorption characteristics. Conclusions: The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10-20 μg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.",
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author = "Birmingham, {Patrick K} and Tobin, {Michael J.} and Henthorn, {Thomas K.} and Fisher, {Dennis M.} and Berkelhamer, {Maura C.} and Smith, {Frederick A.} and Fanta, {Kaaren B.} and Cot{\'e}, {Charles J.}",
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Birmingham, PK, Tobin, MJ, Henthorn, TK, Fisher, DM, Berkelhamer, MC, Smith, FA, Fanta, KB & Coté, CJ 1997, 'Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: An old drug with new recommendations', Anesthesiology, vol. 87, no. 2, pp. 244-252. https://doi.org/10.1097/00000542-199708000-00010

Twenty-four-hour pharmacokinetics of rectal acetaminophen in children : An old drug with new recommendations. / Birmingham, Patrick K; Tobin, Michael J.; Henthorn, Thomas K.; Fisher, Dennis M.; Berkelhamer, Maura C.; Smith, Frederick A.; Fanta, Kaaren B.; Coté, Charles J.

In: Anesthesiology, Vol. 87, No. 2, 22.10.1997, p. 244-252.

Research output: Contribution to journalArticle

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T1 - Twenty-four-hour pharmacokinetics of rectal acetaminophen in children

T2 - An old drug with new recommendations

AU - Birmingham, Patrick K

AU - Tobin, Michael J.

AU - Henthorn, Thomas K.

AU - Fisher, Dennis M.

AU - Berkelhamer, Maura C.

AU - Smith, Frederick A.

AU - Fanta, Kaaren B.

AU - Coté, Charles J.

PY - 1997/10/22

Y1 - 1997/10/22

N2 - Background: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. Methods: Children (n = 28) were randomized to receive a single dose of 10, 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 for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. Results: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 μg/nd serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml · kg-1 · min-1. Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption from the rectum. Suppository dose size also may affect absorption characteristics. Conclusions: The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10-20 μg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.

AB - Background: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. Methods: Children (n = 28) were randomized to receive a single dose of 10, 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 for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. Results: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 μg/nd serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml · kg-1 · min-1. Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption from the rectum. Suppository dose size also may affect absorption characteristics. Conclusions: The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10-20 μg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.

KW - Analgesics: acetaminophen

KW - Anesthesia: pediatric

KW - Pharmacokinetics: modelling

KW - Pharmacology: acetaminophen; rectal

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