Mahoney Liam, Shah Geetika, Crook David, Rojas-Anaya Hector, Rabe Heike
Academic Department of Paediatrics, Brighton and Sussex Medical School, Royal Alexandra Children's Hospital, Level 6, Room 663, Eastern Road, Brighton, BN2 5BE, UK.
Clinical Investigation and Research Unit, Royal Sussex County Hospital, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
Pediatr Cardiol. 2016 Jan;37(1):14-23. doi: 10.1007/s00246-015-1263-9. Epub 2015 Sep 7.
Since its discovery in 1975 dobutamine has been used off-label for treating hemodynamic insufficiency in newborns and children. We present a structured literature review of pharmacokinetic and pharmacodynamic data for dobutamine in the pediatric population. Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria. Where possible, results for the pharmacodynamic and pharmacokinetic effect of dobutamine were reported as pooled data. Forty-six papers met the inclusion criteria. With regard to pharmacodynamic data a number of studies reported significant increases in a number of clinical parameters such as heart rate, blood pressure, cardiac output across a wide range of pediatric populations. With regard to pharmacokinetic data studies reported that the infusion rate was positively correlated to plasma dobutamine concentration. There was great variability with regard to dobutamine clearance between individuals and as to whether it followed first- or zero-order elimination kinetics. While the pharmacodynamic effects of dobutamine appear to reflect the pharmacological profile of the drug, the pharmacokinetic data are difficult to interpret due to inhomogeneity between study populations ages, comorbidities, dobutamine dosages and methodologies. High-quality prospective pharmacokinetic and pharmacodynamic data especially in newborns are urgently required prior to a large randomized study.
自1975年被发现以来,多巴酚丁胺一直被用于治疗新生儿和儿童血流动力学不足,但属于超说明书用药。我们对儿科人群中多巴酚丁胺的药代动力学和药效学数据进行了结构化文献综述。根据预先定义的纳入标准进行结构化检索,以识别相关文章。在可能的情况下,多巴酚丁胺的药效学和药代动力学效应结果以汇总数据形式报告。46篇论文符合纳入标准。关于药效学数据,多项研究报告称,在广泛的儿科人群中,心率、血压、心输出量等多项临床参数显著增加。关于药代动力学数据,研究报告称输注速率与血浆多巴酚丁胺浓度呈正相关。个体之间多巴酚丁胺清除率以及其遵循一级还是零级消除动力学存在很大差异。虽然多巴酚丁胺的药效学效应似乎反映了该药物的药理学特征,但由于研究人群在年龄、合并症、多巴酚丁胺剂量和方法学方面存在异质性,药代动力学数据难以解释。在进行大型随机研究之前,迫切需要高质量的前瞻性药代动力学和药效学数据,尤其是新生儿的数据。