Clinical Pharmacology of Intravenous Paracetamol in Neonates

Karel Allegaert*, 1, Marc van de Velde2, Gunnar Naulaers1
1 Neonatal Intensive Care Unit and
2 Department of Anaesthesiology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium

Article Metrics

CrossRef Citations:
Total Statistics:

Full-Text HTML Views: 158
Abstract HTML Views: 849
PDF Downloads: 566
Total Views/Downloads: 1573
Unique Statistics:

Full-Text HTML Views: 124
Abstract HTML Views: 584
PDF Downloads: 421
Total Views/Downloads: 1129

Creative Commons License
Allegaert et al.; Licensee Bentham Open

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Neonatal Intensive Care Unit, Division of Woman and Child, University Hospitals Leuven, campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium; Tel: 00-32-16-343210; Fax: 00-32-16-343209; E-mail:


Effective analgesia in neonates is still hampered due to the lack of data on pharmacokinetics and –dynamics of analgesics in this specific population. To a certain extent, this is even true for paracetamol. An intravenous formulation might improve prediction of concentration and consequent effect compared to enteral administration. In this review, we summarize the consecutive steps reported in literature to document the pharmacokinetics, metabolism and hepatic tolerance of intravenous paracetamol in neonates.

Based on a single intravenous dose study, pharmacokinetics estimates were calculated and a repeated dose regimen was developed. This dose regimen was subsequently evaluated in a repeated dose study, and paracetamol metabolism was described during repeated dose administration. Finally, hepatic tolerance in neonates was documented.

Based on the available pharmacokinetic estimates, it seems that intravenous paracetamol is an attractive analgesic to be used in neonates, as an alternative or add-on therapy for opioid administration. After the documentation of the pharmacokinetics of paracetamol in neonates and in the absence of any data on pharmacodynamics of intravenous paracetamol in this population, prospective, well designed and appropriated powered pharmacodynamic studies in neonates are urgently needed.