Pharmacokinetics and safety of prolonged paracetamol treatment in neonates: An interventional cohort study
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Aims: To investigate the pharmacokinetics and safety of prolonged paracetamol use (>72 h) for neonatal pain. Methods: Neonates were included if they received paracetamol orally or intravenously for pain treatment. A total of 126 samples were collected. Alanine aminotransferase and bilirubin were measured as surrogate liver safety markers. Paracetamol and metabolites were measured in plasma. Pharmacokinetic parameters for the parent compound were estimated with a nonlinear mixed-effects model. Results: Forty-eight neonates were enrolled (38 received paracetamol for >72 h). Median gestational age was 38 weeks (range 25–42), and bodyweight at inclusion was 2954 g (range 713–4750). Neonates received 16 doses (range 4–55) over 4.1 days (range 1–13.8). The median (range) dose was 10.1 mg/kg (2.9–20.3). The median oxidative metabolite concentration was 14.6 μmol/L (range 0.12–113.5) and measurable >30 h after dose. There was no significant difference (P >.05) between alanine aminotransferase and bilirubin measures at <72 h or >72 h of paracetamol treatment or the start and end of the study. Volume of distribution and paracetamol clearance for a 2.81-kg neonate were 2.99 L (% residual standard error = 8, 95% confidence interval 2.44–3.55) and 0.497 L/h (% residual standard error = 7, 95% confidence interval 0.425–0.570), respectively. Median steady-state concentration from the parent model was 50.3 μmol/L (range 30.6–92.5), and the half-life was 3.55 h (range 2.41–5.65). Conclusion: Our study did not provide evidence of paracetamol-induced liver injury nor changes in metabolism in prolonged paracetamol administration in neonates.
Original language | English |
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Journal | British Journal of Clinical Pharmacology |
Volume | 89 |
Issue number | 11 |
Pages (from-to) | 3421-3431 |
Number of pages | 11 |
ISSN | 0306-5251 |
DOIs | |
Publication status | Published - Nov 2023 |
Bibliographical note
Funding Information:
To the project nurses in the NICUs—Christel Friborg, Madeleine Borgen and Lene Bøjgaard Bak—we could not have done this without you. Thank you for your dedication and the talented way you connected the study with the 2 sites. The bioanalytical staff from both sites also contributed with very valuable insights and practical help with samples. This study was funded by the Danish Regions.
Funding Information:
We would like to thank Steen Hertel, former Head of the Department of Neonatology in Rigshospitalet. He was a huge inspiration for the conception of the study and participated as primary investigator in the first part of the study before he retired. To the project nurses in the NICUs—Christel Friborg, Madeleine Borgen and Lene Bøjgaard Bak—we could not have done this without you. Thank you for your dedication and the talented way you connected the study with the 2 sites. The bioanalytical staff from both sites also contributed with very valuable insights and practical help with samples. This study was funded by the Danish Regions.
Publisher Copyright:
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
- acetaminophen, neonates, pain, paracetamol, pharmacokinetics
Research areas
ID: 373475167