652: OXYGENATOR IMPACT ON REMDESIVIR IN EXTRACORPOREAL MEMBRANE OXYGENATION CIRCUITS
Critical care medicine(2022)
Abstract
Introduction: Extra-corporeal membrane oxygenation (ECMO) is a treatment modality known to alter drug pharmacokinetics (PK). The PK changes can result from drug binding to the oxygenator, alterations in clearance, and drug adsorption or sequestration. Levels of drug absorption by polymers, silicone rubber and other materials have been linked to the drugs’ lipophilicity and the published literature is mostly outdated. Additionally, there is limited data regarding the impact of the oxygenator on drug changes in ECMO circuits in comparison to the other components of the ECMO circuit. The purpose of this study was to determine the impact of the Quadrox-i pediatric and adult oxygenators on the PK of remdesivir (RDV) in contemporary ECMO circuits. Methods: One 1/4-in. and one 3/8-in. closed loop ECMO circuits were prepared using custom tubing with polyvinylchloride and superTygon® (Medtronic Inc., Minneapolis, MN) and a Quadrox-i adult or pediatric oxygenator (Maquet). Additionally, one 1/4-in. and one 3/8-in. closed loop ECMO circuits were assembled without an oxygenator in series. RDV was added to the circuit and levels were obtained pre-and post-oxygenator at the following time intervals; 5 mins, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hrs. RDV was also maintained in a glass vial and samples obtained at the same time periods for control purposes. RDV samples were analyzed by liquid chromatography tandem mass spectrometry. Results: For the 3/8-in. circuit with and without an oxygenator, there was a 60-70% RDV loss during the study period. For the 1/4-in. circuits with an oxygenator, there was a 35-60% RDV loss during the study period. For the 1/4-in. circuits without an oxygenator, there was a 5-20% RDV loss during the study period. Conclusions: There was RDV loss within the circuit during the study period and the RDV loss was more pronounced with the larger 3/8-in circuit when compared with the 1/4-in. circuit. This preliminary data suggests 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.
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