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

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 (AUC(0-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 AUC(0-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 (C(max)) 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 C(max) is delayed by half an hour after intranasal administration. TRIAL REGISTRATION NUMBER: NCT03059511.