PT  - JOURNAL ARTICLE
AU  - Pfiffner, Miriam
AU  - Gotta, Verena
AU  - Pfister, Marc
AU  - Vonbach, Priska
AU  - Berger-Olah, Eva
TI  - Pharmacokinetics and tolerability of intranasal or intravenous administration of nalbuphine in infants
AID  - 10.1136/archdischild-2022-323807
DP  - 2023 Jan 01
TA  - Archives of Disease in Childhood
PG  - 56--61
VI  - 108
IP  - 1
4099  - http://adc.bmj.com/content/108/1/56.short
4100  - http://adc.bmj.com/content/108/1/56.full
SO  - Arch Dis Child2023 Jan 01; 108
AB  - 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.Data are available upon reasonable request.