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

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 (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.