The following is a summary of “Edoxaban pharmacokinetics during in vitro continuous renal replacement therapy,” published in the October 2024 issue of Nephrology by Wenzler et al.
Researchers conducted a prospective study to evaluate edoxaban clearance during in vitro continuous renal replacement therapy.
They added edoxaban to the CRRT circuit and collected pre-filter bovine blood, post-filter blood, and effluent samples. Experiments were conducted in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes with varying filter types, flow rates, and dilution points. Edoxaban and urea concentrations were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters were estimated using noncompartmental analysis, while 2- and 3-way ANOVA assessed the effects of mode, filter type, flow rate, and dilution on CLCRRT. Linear regression provided dosing estimations for effluent flow rates from 0.5 to 5 L/h, suggesting optimal edoxaban doses CLCRRT and population non-renal clearance (CLNR) to match the systemic AUC for venous thromboembolism treatment efficacy.
The results showed that edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, with a mean percent protein binding of 41%. Multivariate analyses confirmed that CRRT mode, filter type, and point of dilution did not influence the CLCRRT of edoxaban, allowing dosing recommendations based on effluent flow rate. Doses of 30-45 mg once daily were estimated to achieve the target AUC threshold for flow rates from 0.5 to 5 L/h.
Investigators concluded that an edoxaban dose of 45 mg once daily is expected to meet target systemic exposure thresholds for venous thromboembolism treatment at commonly used CRRT flow rates, necessitating further clinical investigation into its safety and efficacy.
Source: bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03777-7#Abs1