Hospital Pharmacy, University Children's Hospital Zurich, Zurich, Switzerland
Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.
Arch Dis Child. 2023 Jan;108(1):56-61. doi: 10.1136/archdischild-2022-323807. Epub 2022 Sep 13.
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.
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) 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.
Out of 52 study subjects receiving nalbuphine, 31 were eligible for NCA (11 intravenous, 20 intranasal). Median AUC 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) 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.
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 is delayed by half an hour after intranasal administration.
NCT03059511.
纳布啡经鼻给药可作为婴儿患者一种安全、有效且非侵入性的替代选择，用于治疗注射用止痛药。本研究旨在评估纳布啡经鼻和静脉给药在婴儿患者中的药代动力学（PK）和耐受性。
本前瞻性开放标签研究纳入了年龄在 1-3 个月大的因接受程序性疼痛管理而入住急诊室的婴儿患者，为他们单次使用 0.05mg/kg 的纳布啡静脉注射或 0.1mg/kg 的纳布啡经鼻给药。在给药后 15、30 和 120-180 分钟采集纳布啡 PK 样本。通过非房室分析（NCA）计算曲线下面积（AUC），并通过 Wilcoxon 检验进行比较。在纳布啡给药期间以及进行静脉通路建立、导尿和腰椎穿刺等干预措施时，使用新生儿疼痛评分（NIPS）进行评估。
在接受纳布啡治疗的 52 名研究对象中，有 31 名符合 NCA 条件（11 名静脉注射，20 名经鼻）。静脉注射 0.05mg/kg 纳布啡后的 AUC 中位数为 8.7（IQR：8.0-18.6）µg×L/hour，而经鼻给予 0.1mg/kg 纳布啡后的 AUC 中位数为 7.6（5.4-10.4）µg×L/hour（p=0.091）。经鼻给药后 30 分钟时观察到最大血清浓度（C）（3.5-5.6µg/L）。静脉注射和经鼻纳布啡给药期间，分别有 71%和 67%的研究对象记录到轻度至无疼痛。
这是第一项研究婴儿经鼻给予纳布啡的研究，表明经鼻给药的生物利用度接近 50%。非侵入性经鼻应用具有良好的耐受性。需要进一步的研究来优化剂量和干预时间，因为经鼻给药后 C 延迟了半小时。
NCT03059511。
