Pellicer Adelina, Fernández Ramón, Jullien Vincent, Gleeson Clare, Bravo María Carmen, Ortego Paloma López, Sánchez Laura, Ybarra Marta, Rojas-Anaya Héctor, Cabañas Fernando, Koch Armin, Smith Andrea, Rabe Heike
Neonatology Group, IdiPAZ, Madrid, Spain.
Department of Neonatology, La Paz University Hospital (HULP), Madrid, Spain.
Pediatr Res. 2021 Mar;89(4):981-986. doi: 10.1038/s41390-020-1009-0. Epub 2020 Jul 1.
Dobutamine is particularly suited to treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in the preterm infant. Knowledge of the elimination half-life is essential to estimate the steady state when its efficacy/safety can be evaluated.
Analysis of pharmacokinetic data in ten preterm newborns treated with a new neonatal formulation of dobutamine (IMP) after screening for haemodynamic insufficiency within the first 72 h from birth. Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h). IMP concentration in each sample was measured by ultra-high performance liquid chromatography with electrochemical detection.
Median duration of IMP infusion was 37.7 h (IQR 21.2). Calculated IMP half-life ranged between 3.06 and 36.1 min (median 10.6 min), leading to a time to reach the steady-state concentration between 15 min and >2 h. Adverse events were not related to IMP.
The wide variability in dobutamine metabolism in preterm infants requires awareness about the risk of under- or overtreatment. A delay of up to 3 h might be required before drawing blood samples to evaluate the effective dose.
Small trials suggest dobutamine as the optimal drug in the preterm infant with haemodynamic insufficiency after birth. Age-related differences in drug pharmacokinetics may result in suboptimal treatments. The lack of formal studies in preterms results in inadequate data on efficacy and safety. This study provides data on the variability of the elimination half-life of dobutamine in the very preterm infant during transitional circulation. There is a wide variation in the time to reach the plasma concentration corresponding to steady state, the moment when its efficacy/safety can be reliably evaluated. This information is crucial for planning future trials on cardiovascular support.
多巴酚丁胺特别适用于治疗早产儿因外周血管阻力增加和心肌功能障碍引起的血流动力学不足。了解消除半衰期对于评估其疗效/安全性时估计稳态至关重要。
对出生后72小时内筛查出血流动力学不足的10例早产新生儿使用新的新生儿剂型多巴酚丁胺（IMP）治疗后的药代动力学数据进行分析。在IMP输注结束时以及输注结束后的随机时间（5分钟、15分钟、45分钟、2小时和6小时）采集血样。通过超高效液相色谱-电化学检测法测量每个样本中的IMP浓度。
IMP输注的中位持续时间为37.7小时（四分位间距21.2）。计算得出的IMP半衰期在3.06至36.1分钟之间（中位数为10.6分钟），达到稳态浓度的时间在15分钟至2小时以上。不良事件与IMP无关。
早产儿多巴酚丁胺代谢的广泛变异性需要意识到治疗不足或过度治疗的风险。在采集血样评估有效剂量之前可能需要长达3小时的延迟。
小型试验表明多巴酚丁胺是出生后有血流动力学不足的早产儿的最佳药物。药物药代动力学的年龄相关差异可能导致治疗效果不佳。缺乏对早产儿的正式研究导致疗效和安全性数据不足。本研究提供了极早产儿在过渡循环期间多巴酚丁胺消除半衰期变异性的数据。达到与稳态相对应的血浆浓度的时间存在很大差异，而在稳态时其疗效/安全性可以得到可靠评估。这些信息对于规划未来的心血管支持试验至关重要。
