Antiviral Dosing Modification for Coronavirus Disease 2019–Infected Patients Receiving Extracorporeal Therapy

Abstract

Previous literature regarding coronavirus disease 2019 outlined a presence of organ dysfunction including acute respiratory distress syndrome and acute kidney injury that are linked to mortality. Several patients require extracorporeal therapy. This review aims to gather available published resources including physicochemical and pharmacokinetic properties and suggests antiviral drug dosing adaptation for coronavirus disease 2019–infected critically ill patients receiving extracorporeal therapy. A literature search was performed using PubMed, clinical trial registries, and bibliographic review of textbooks and review articles. Unfortunately, no standard of pharmacologic management and recommendations of drug dosing for coronavirus disease 2019 infection for critically ill patients receiving extracorporeal therapy exist due to the limited data on pharmacokinetic and clinical studies. All available extracted data were analyzed to suggest the appropriate drug dosing adjustment. Antiviral drug dosing adjustments for critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy are presented in this review. Considering pathophysiologic changes, drug properties, and extracorporeal modalities, applying our suggestions is recommended.

Molecular docking, binding mode analysis, molecular dynamics, and prediction of ADMET/toxicity properties of selective potential antiviral agents against SARS-CoV-2 main protease: an effort toward drug repurposing to combat COVID-19

“…A study by Warhurst et al 2003 reported experimental log P of HCQ (3.84 ± 0.2) and CQ (4.72), which were in good agreement with their calculated ClogP values and ∼0.30 ± 0.04 log units lower than the calculated ClogP value [65]. The log P of the RDV and GS441524 is 1.8 and 1.65, respectively, which are in good agreement with their calculated ClogP values, but a significant variation was observed in the case of GS441524 with − 3.84 log units higher than the calculated ClogP [66]. On the contrary, GA undergoes presystemic biotransformation after oral administration to glycyrrhetinic acid (GLA); therefore, most of the clinical pharmacokinetic studies are published on GLA.…”

Population pharmacokinetic modeling of GS‐441524, the active metabolite of remdesivir, in Japanese COVID‐19 patients with renal dysfunction

“… 12 , 13 Remdesivir was considered to have a moderate possibility to be lost via the ECMO circuit owing to calculated logP and protein binding. 14 To the best of our knowledge, there is a lack of PK data in patients with COVID‐19 in specific populations owing to limited information of clinical trials and inexperienced clinical use.…”

Kidney implications of SARS-CoV2 infection in children

“…One study has assessed the role of TPE in critically ill children with COVID-19 and MIS-C ( n = 27); those who received TPE had a rapid improvement in left ventricular ejection fraction and decrease in pediatric logistic organ dysfunction (PELOD) scores [ 31 ]. Additional guidelines have considered the effect of extracorporeal clearance of newer therapies against COVID-19, such as remdesivir [ 32 ].…”