【原】【罂粟摘要】婴儿鼻内或静脉给予纳布啡的药代动力学和耐受性

婴儿鼻内或静脉给予纳布啡的药代动力学和耐受性

贵州医科大学    麻醉与心脏电生理课题组

翻译：邓举          编辑：宋雨婷       审校：曹莹

目的

鼻内给予纳布啡可能是一种安全、有效、无创、可替代婴儿肠道外给药的方式。本研究目的是评估婴儿鼻内和静脉给予纳布啡的药代动力学（PK）和耐受性。

方法

这项前瞻性开放性研究纳入1-3个月且接受纳布啡进行程序性疼痛管理的婴儿。将患儿分为静脉组（静脉注射0.05mg/kg纳布啡）和鼻内组（鼻内给予0.1mg/kg纳布啡）。给药后15、30、120~180 min采集纳布啡PK样品。采用非室间分析（NCA）计算浓度时间曲线下面积（AUC_0-Tlast），并采用Wilcoxon检验进行比较。在纳布啡给药和以下干预措施中评估患儿疼痛评分，干预措施包括建立静脉通路、导尿、腰椎穿刺。

结果

在52名接受纳布啡的受试者中，31名符合NCA的条件（11名静脉注射，20名鼻内注射）。静脉注射0.05mg/kg后的平均AUC_0-Tlast为8.7 (IQR：8.0-18.6）µg×L/h，而鼻内注射0.1mg/kg后为7.6（5.4-10.4）µg×L/h（P =0.091）。在鼻内给药30 min后，观察到最高血清浓度（C_max）为3.5-5.6µg/L。在静脉注射和鼻内给予纳布啡期间，分别有71%和67%的受试者记录了轻度疼痛到无疼痛。

结论

本研究为第一个调查婴儿鼻内注射纳布啡的研究，表明鼻内生物利用度接近50%。无创鼻内应用的耐受性良好。由于C_max在鼻内给药后会延迟半小时，需要更多的研究来优化给药和干预时间。

原始文献来源

Miriam Pfiffner , Verena Gotta, Marc Pfister,et al.Pharmacokinetics and tolerability of intranasal or intravenous administration of nalbuphine in infants［J］.Arch Dis Child 2023;108:56–61.

英文原文

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.