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 0.05mg/kg intravenously or 0.1mg/kg intranasally. Nalbuphine PK samples were collected 15, 30 and 120–180min 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 AUC0-Tlast after 0.05mg/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 0.1mg/kg (p=0.091). Maximum serum concentration (C_max) was observed 30min 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.