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Drug therapy
Pharmacokinetics and tolerability of intranasal or intravenous administration of nalbuphine in infants
  1. Miriam Pfiffner1,
  2. Verena Gotta2,
  3. Marc Pfister2,
  4. Priska Vonbach3,
  5. Eva Berger-Olah4
  1. 1 Hospital Pharmacy, University Children’s Hospital Zurich, Zurich, Switzerland
  2. 2 Pediatric Pharmacology and Pharmacometrics, University of Basel Children’s Hospital, Basel, Switzerland
  3. 3 PEDeus, a subsidiary of the University Children’s Hospital Zurich, Zurich, Switzerland
  4. 4 Emergency Unit, University Children’s Hospital Zurich, Zurich, Switzerland
  1. Correspondence to Miriam Pfiffner, Hospital Pharmacy, Universitäts-Kinderspital Zürich, Zurich 8032, Switzerland; miriam.pfiffner{at}kispi.uzh.ch

Abstract

Objectives Intranasal nalbuphine could be a safe, efficacious and non-invasive alternative to parenteral pain medication in infants. We aimed to assess pharmacokinetics (PK) and tolerability of intranasal and intravenous nalbuphine administration in infants.

Methods Prospective open-label study including infants 1–3 months of age admitted to the emergency department, receiving nalbuphine for procedural pain management. Patients were alternately allocated to a single nalbuphine dose of 0.05 mg/kg intravenously or 0.1 mg/kg intranasally. Nalbuphine PK samples were collected 15, 30 and 120–180 min after dosing. Area under the concentration time curve (AUC0-Tlast) was calculated by non-compartmental analysis (NCA) and compared by Wilcoxon test. Neonatal Infant Pain Score was assessed during nalbuphine administration and the following interventions: venous access, urinary catheterisation, lumbar puncture.

Results Out of 52 study subjects receiving nalbuphine, 31 were eligible for NCA (11 intravenous, 20 intranasal). Median AUC0-Tlast after 0.05 mg/kg intravenously was 8.7 (IQR: 8.0–18.6) µg×L/hour vs 7.6 (5.4–10.4) µg×L/hour after intranasal administration of 0.1 mg/kg (p=0.091). Maximum serum concentration (Cmax) was observed 30 min after intranasal administration (3.5–5.6 µg/L). During intravenous and intranasal nalbuphine administration, mild to no pain was recorded in 71% and 67% of study subjects, respectively.

Conclusion This is the first study investigating intranasal administration of nalbuphine in infants suggesting an intranasal bioavailability close to 50%. Non-invasive intranasal application was well tolerated. Additional studies are warranted to optimise dosing and timing of interventions as Cmax is delayed by half an hour after intranasal administration.

Trial registration number NCT03059511.

  • pain
  • paediatric emergency medicine

Data availability statement

Data are available upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/archdischild-2022-323807

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • Twitter @PVonbach

    • MP and VG contributed equally.

    • Contributors MPfiffner—conceptualisation/design, methodology, data curation, investigation, formal analysis, writing (drafting the initial manuscript), final approval of the version to be published. VG—data curation, formal analysis, supervision/oversight, writing (review or editing of the manuscript), final approval of the version to be published. PV—conceptualisation/design, methodology, funding acquisition, supervision/oversight, resources, writing (review or editing of the manuscript), final approval of the version to be published. MPfister—conceptualisation/design, methodology, funding acquisition, supervision/oversight, resources, writing (review or editing of the manuscript), final approval of the version to be published. EB-O—conceptualisation/design, methodology, data curation, investigation, supervision/oversight, resources, writing (review or editing of the manuscript), final approval of the version to be published.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.