Department of Neonatology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Acta Paediatr. 2018 Feb;107(2):249-254. doi: 10.1111/apa.14018. Epub 2017 Sep 4.
Piglets models have often been used to study the effects of dopamine infusion on hypotension in neonates. However, piglets need higher doses of dopamine than neonates to increase blood pressure. We investigated whether this difference was due to interspecific difference in dopamine pharmacokinetics.
Arterial blood samples were drawn from six neonates admitted to the neonatal intensive care unit of Copenhagen University Hospital and 20 newborn piglets during continuous dopamine infusion. Furthermore, to estimate the piglet plasma dopamine half-life, blood samples were drawn at 2.5-minute intervals after the dopamine infusion was discontinued. The plasma dopamine content was analysed by high-performance liquid chromatography with electrochemical detection.
The dopamine displayed first-order kinetics in piglets and had a half-life of 2.5 minutes, while the median plasma clearance was 627.9 mL/kg/minute (interquartile range 452.6-1914.4). Both piglets and neonates showed large interindividual variations in plasma clearance, but the median tended to be lower in neonates (384.9, interquartile range 114.2-480.2 mL/kg/minute).
Our results suggest that pharmacokinetic differences may explain the interspecific difference in required doses of dopamine infusion to increase blood pressure. This is important when translating the results obtained in piglet models to treating neonatal hypotension with dopamine.
仔猪模型常用于研究多巴胺输注对新生儿低血压的影响。然而，与新生儿相比，仔猪需要更高剂量的多巴胺来升高血压。我们研究了这种差异是否是由于多巴胺药代动力学的种间差异所致。
在哥本哈根大学医院新生儿重症监护病房入院的 6 名新生儿和 20 名新生仔猪连续输注多巴胺期间，从动脉血样中抽取。此外，为了估计仔猪血浆多巴胺半衰期，在停止多巴胺输注后以 2.5 分钟的间隔抽取血样。通过高效液相色谱法和电化学检测分析血浆多巴胺含量。
多巴胺在仔猪中呈一级动力学，半衰期为 2.5 分钟，而中位数血浆清除率为 627.9 mL/kg/min（四分位距 452.6-1914.4）。仔猪和新生儿的血浆清除率均存在较大的个体间差异，但中位数在新生儿中较低（384.9，四分位距 114.2-480.2 mL/kg/min）。
我们的结果表明，药代动力学差异可能解释了增加血压所需的多巴胺输注剂量的种间差异。这在将仔猪模型中获得的结果转化为用多巴胺治疗新生儿低血压时很重要。
