Pharmacokinetics and tolerability of intranasal or intravenous administration of nalbuphine in infants

• Published in: Archives of disease in childhood Vol. 108; no. 1; pp. 56 - 61
• Main Authors: Pfiffner, Miriam, Gotta, Verena, Pfister, Marc, Vonbach, Priska, Berger-Olah, Eva
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health 01.01.2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Administration, Intranasal; Administration, Intravenous; Analgesics; Anatomy; Bioavailability; Biological Availability; Body Weight; Clinical medicine; Concentration time; Diagnostic tests; Dosage; Drug dosages; Drug Therapy; Emergency medical care; Fentanyl; Guidelines; Humans; Infant; Infants; Intervention; Intranasal administration; Intravenous administration; Licenses; Nalbuphine - administration & dosage; Nalbuphine - adverse effects; Narcotics; Neonates; paediatric emergency medicine; Pain; Pain - drug therapy; Pain - etiology; Patients; Pediatrics; Pharmacokinetics; Pharmacology; Prospective Studies; Sample size; Sampling; Scientific Concepts; Venous access; Vital signs; Young Children; United States > US; Switzerland; paediatric emergency medicine; pain
• ISSN: 0003-9888; 1468-2044; 1468-2044
• DOI: 10.1136/archdischild-2022-323807

ObjectivesIntranasal 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.MethodsProspective 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.ResultsOut 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.ConclusionThis 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.