Samiee-Zafarghandy Samira, van Donge Tamara, Fusch Gerhard, Pfister Marc, Jacob George, Atkinson Andrew, Rieder Michael J, Smit Cornelis, Van Den Anker John
Division of Neonatology, McMaster Children's Hospital, Hamilton, Ontario, Canada
Department of Pediatric Pharmacology and Pharmacometrics, UKBB Universitäts-Kinderspital, Basel, Switzerland.
Arch Dis Child. 2022 Jan;107(1):86-91. doi: 10.1136/archdischild-2020-321381. Epub 2021 May 11.
Exploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.
Prospective, single-centre, open-label, pharmacokinetics study in preterm neonates.
Neonatal intensive care unit at McMaster Children's Hospital.
Neonates with a gestational age ≤28 weeks treated with oral ibuprofen for closure of a PDA.
Population pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.
Association between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC >900 mg·hour/L).
Twenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours' postdose on the first day, a strong correlation between ibuprofen concentrations and AUC was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure.
We designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.
探索一种新型治疗药物监测（TDM）策略，以实现布洛芬在早产儿动脉导管未闭（PDA）闭合治疗中的个体化应用。
对早产儿进行的前瞻性、单中心、开放标签的药代动力学研究。
麦克马斯特儿童医院新生儿重症监护病房。
胎龄≤28周且接受口服布洛芬治疗PDA闭合的新生儿。
采用药代动力学建模与模拟获得群体药代动力学参数、浓度-时间曲线和暴露指标。
治疗第一天不同采样时间点测得的布洛芬血浆浓度与治疗前3天达到目标暴露量（AUC>900mg·小时/L）之间的关联。
纳入23例早产儿（中位出生体重780g，胎龄25.9周），共获得155份布洛芬血浆样本。从治疗第一天给药后8小时开始，观察到布洛芬浓度与AUC之间存在强相关性。首剂给药后8小时，布洛芬浓度>20.5mg/L与达到目标暴露量的概率为90%相关。
我们设计了一种新颖且实用的TDM策略，并表明在治疗第一天采集单个样本即可预测达到目标暴露量（AUC>900mg·小时/L）的可能性。这一新获得的知识可用于个体化布洛芬给药方案，并提高布洛芬用于PDA药物闭合的疗效。
