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  • Open Access

Intravenous paracetamol pharmacokinetics in neonates: a pooled analysis

  • 1,
  • 2 and
  • 3
Critical Care201115 (Suppl 1) :P346

https://doi.org/10.1186/cc9766

  • Published:

Keywords

  • Paracetamol
  • Linear Disposition
  • Unconjugated Bilirubin
  • Population Parameter Estimate
  • Intravenous Paracetamol

Introduction

The aim of this study was to describe paracetamol pharmacokinetics in neonates, to determine its covariates and suggest a dosing regimen for neonates (28 to 44 weeks postmenstrual age (PMA)).

Methods

A population PK analysis of paracetamol time-concentration profiles (943 observations) from 158 neonates (27 to 45 weeks PMA) was undertaken using nonlinear mixed-effects models. Data from three earlier published studies involving neonates given either i.v. propacetamol or paracetamol were pooled with newly collected observations during repeated i.v. paracetamol administration (n = 60, 343 observations, PARANEO study) [13].

Results

A two-compartment linear disposition model was used. Population parameter estimates (between-subject variability, %) were central volume (V1) 51.9 (21.6%) l/70 kg, peripheral volume of distribution (V2) 22.7 l/70 kg, clearance (CL) 5 (40%) l/hour/70 kg and inter-compartment clearance (Q) 16.2 l/hour/70 kg. About one-half (60.9%) of the overall CL variance is predictable from covariates. Weight was used to predict size and this was the major covariate (57.5%). Clearance expressed as mg/kg/hour increases only slightly with PMA (0.138 at 28 weeks, 0.167 l/hour/kg at 44 weeks PMA), contributing only 2.2% of variance within this cohort. Unconjugated bilirubin contributed only an additional 1.2% of variance.

Conclusions

An increased volume of distribution supports the use of a loading dose when instigating paracetamol therapy in neonates while size is the major covariate of clearance. Clearance matured slowly in this cohort and a mean paracetamol serum concentration of 11 mg/l is achieved in neonates (28 to 44 weeks) given a standard dose of paracetamol of 10 mg/kg/6 hours. Based on these estimates, we suggest a loading dose of 20 mg/kg followed by 6-hourly dosing (10 mg/kg) within the age range evaluated.

Authors’ Affiliations

(1)
University Hospitals Leuven, Belgium
(2)
Royal Children's Hospital, Melbourne, Australia
(3)
University of Auckland, New Zealand

References

  1. Allegaert K, et al.: Arch Dis Child Fetal Neonatal Ed. 2004, 89: F25-F28. 10.1136/fn.89.1.F25PubMed CentralView ArticlePubMedGoogle Scholar
  2. Allegaert K, et al.: Eur J Clin Pharmacol. 2004, 60: 191-197. 10.1007/s00228-004-0756-xView ArticlePubMedGoogle Scholar
  3. Palmer G, et al.: Br J Anaesth. 2008, 101: 523-530. 10.1093/bja/aen208View ArticlePubMedGoogle Scholar

Copyright

© Allegaert et al. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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