Background

Enteral ibuprofen was first approved as a prescription drug in 1974 for the US market. An intravenous (IV) ibuprofen formulation is approved for use in children older than 6 months of age, but there are limited studies specifically evaluating the pharmacokinetics and safety in children 1–6 months of age.

Aims

The primary purpose of this study was to evaluate the pharmacokinetics of IV ibuprofen in infants younger than 6 months of age. The secondary objective was to evaluate the safety of single and repeated doses of IV ibuprofen in infants younger than 6 months of age.

Methods

This was an industry-sponsored multi-center study. Institutional Review Board approval and informed parental consent were obtained prior to enrollment. Hospitalized neonates and infants younger than 6 months of age with fever or expected postoperative pain were eligible. Enrolled patients received 10 mg/kg of IV ibuprofen every 6 h, with up to four doses per day. Patients were randomized to two sparse sampling technique pharmacokinetic sample time groups. Group 1 samples were drawn at 0, 30 min, and 2 h, while group 2 samples were drawn at 0 min, 1, and 4 h after administration.

Results

A total of 24 children were enrolled in the study, with 15 male patients and 9 female patients. The median age of the cohort was 4.4 months (range 1.1–5.9 months), and the median weight was 5.9 kg (range 2.3–8.8 kg). The arithmetic mean and standard error for peak plasma ibuprofen concentration was 56.28 ± 2.77 µg/mL. Plasma levels declined rapidly with a mean elimination half-life of 1.30 h. Time to peak ibuprofen effect and concentration were similar when compared with older pediatric patients. Clearance and volume of distribution were also similar to those reported in older pediatric patients. No drug-related adverse events were reported.

Conclusions

The pharmacokinetic and short-term safety profiles of IV ibuprofen in pediatric patients 1–6 months of age are comparable to those in children older than 6 months of age.

Trial Registration

Clinicaltrials.gov Trial Registration number and date: NCT02583399—Registered July 2017.

中文翻译：

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1-6 个月婴儿静脉注射布洛芬的药代动力学和安全性的多中心评价

背景

肠内布洛芬于 1974 年首次被批准作为处方药进入美国市场。静脉注射 (IV) 布洛芬制剂被批准用于 6 个月以上儿童，但专门评估 1-6 个月儿童药代动力学和安全性的研究有限。

目标

本研究的主要目的是评估 6 个月以下婴儿静脉注射布洛芬的药代动力学。次要目标是评估 6 个月以下婴儿单次和重复静脉注射布洛芬的安全性。

方法

这是一项由行业赞助的多中心研究。入组前已获得机构审查委员会的批准和家长的知情同意。患有发烧或预期术后疼痛的住院新生儿和 6 个月以下婴儿符合资格。入组患者每 6 小时接受 10 mg/kg 的静脉注射布洛芬，每天最多四剂。患者被随机分为两个稀疏采样技术药代动力学采样时间组。第1组样品在给药后0、30分钟和2小时抽取，而第2组样品在给药后0分钟、1和4小时抽取。

结果

共有 24 名儿童参与研究，其中男性患者 15 名，女性患者 9 名。该队列的中位年龄为 4.4 个月（范围 1.1-5.9 个月），中位体重为 5.9 公斤（范围 2.3-8.8 公斤）。血浆布洛芬浓度峰值的算术平均值和标准误差为 56.28 ± 2.77 µg/mL。血浆水平迅速下降，平均消除半衰期为 1.30 小时。与老年儿科患者相比，布洛芬达到峰值作用的时间和浓度相似。清除率和分布容积也与老年儿科患者报告的相似。没有报告与药物相关的不良事件。

结论

1-6 个月大的儿童患者中静脉注射布洛芬的药代动力学和短期安全性与 6 个月以上儿童的药代动力学和短期安全性相当。

试用注册

ClinicalTrials.gov 试验注册号和日期：NCT02583399 — 2017 年 7 月注册。