Cies Jeffrey J, Moore Wayne S, Deacon Jillian, Enache Adela, Chopra Arun
The Center for Pediatric Pharmacotherapy LLC (JJC, WSM, AC), Pottstown, PA.
St. Christopher's Hospital for Children (JJC, JD), Philadelphia, PA.
J Pediatr Pharmacol Ther. 2024 Jun;29(3):248-254. doi: 10.5863/1551-6776-29.3.248. Epub 2024 Jun 10.
This study aimed to determine the oxygenator impact on alterations of remdesivir (RDV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane -oxygenation (ECMO) circuit including the Quadrox-i oxygenator.
One-quarter-inch and a 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A 1-time dose of RDV was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 0 to 5 minutes, and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-hour time points. The RDV was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation.
For the 1/4-inch circuits with an oxygenator, there was a 35% to 60% RDV loss during the study period. For the 1/4-inch circuits without an oxygenator, there was a 5% to 20% RDV loss during the study period. For the 3/8-inch circuit with and without an oxygenator, there was a 60% to 70% RDV loss during the study period.
There was RDV loss within the circuit during the study period and the RDV loss was more pronounced with the larger 3/8-inch circuit when compared with the 1/4-inch circuit. The impact of the -oxygenator on RDV loss appears to be variable and possibly dependent on the size of the circuit and -oxygenator. These preliminary data suggest RDV dosing may need to be adjusted for concern of drug loss via the ECMO circuit. Additional single- and multiple-dose studies are needed to validate these findings.
本研究旨在确定在当代新生儿/儿科(1/4英寸)和青少年/成人(3/8英寸)体外膜肺氧合(ECMO)回路(包括Quadrox-i氧合器)中,氧合器对瑞德西韦(RDV)变化的影响。
使用Quadrox-i儿科氧合器和Quadrox-i成人氧合器及预充血液,制备1/4英寸和3/8英寸的模拟闭环ECMO回路。此外,还制备了不串联氧合器的1/4英寸和3/8英寸回路。将单次剂量的RDV注入回路,并在0至5分钟以及1、2、3、4、5、6、8、12和24小时时间点获取氧合器前和氧合器后的系列浓度。RDV也保存在玻璃瓶中,并在相同时间段从瓶中取样作为对照,以评估药物的自发降解情况。
对于带有氧合器的1/4英寸回路,在研究期间RDV损失35%至60%。对于不带有氧合器的1/4英寸回路,在研究期间RDV损失5%至20%。对于带有和不带有氧合器的3/8英寸回路,在研究期间RDV损失60%至70%。
在研究期间回路中存在RDV损失,与1/4英寸回路相比,较大的3/8英寸回路中RDV损失更明显。氧合器对RDV损失的影响似乎是可变的,可能取决于回路和氧合器的尺寸。这些初步数据表明,出于对通过ECMO回路造成药物损失的担忧,可能需要调整RDV的给药剂量。需要进行更多的单剂量和多剂量研究来验证这些发现。