In vitro Evaluation of Linezolid and Doripenem Clearance with Different Hemofilters

Abstract

Introduction: Renal replacement therapy (RRT) is widely used in the treatment of septic acute kidney injury. However, little is known about how the adsorption properties of hemofilters used in RRT affect antibiotic concentration. Because a cytokine-adsorption membrane is frequently used in RRT, it is important to determine the antibiotic adsorption capacity of this membrane. Objective: The present study aimed to investigate the antibiotic adsorption capacity of different hemofilter membranes by in vitro experiments using 2 antibacterial agents (linezolid and doripenem). Methods: We performed experimental hemofiltration in vitro using polyacrylonitrile (AN69ST), polymethylmethacrylate (PMMA), and polysulfone (PS) hemofilters for 1,440 min. The test solution was a 1,000-mL substitution fluid containing 30 µg/mL linezolid and 120 µg/mL doripenem. We measured drug concentrations at the inlet, outlet, and filtrate ports of the hemofilters for 1,440 min and calculated the sieving coefficient (SC) and adsorption rate (Ra) of the drugs onto the hemofilters. Results: The amount of linezolid adsorbed onto AN69ST, PMMA, and PS membranes was decreased relative to that in the control group at 15 min (p < 0.05). However, no SC for linezolid was obtained thereafter. The Ra of linezolid onto AN69ST, PMMA, and PS membranes was higher than that in the control group (p < 0.05). In contrast, no significant differences were observed in the concentrations and Ra values of doripenem adsorbed onto AN69ST, PMMA, and PS membranes compared with those in the control group. Conclusions: Doripenem was not adsorbed onto PMMA, PS, and AN69ST membranes. Linezolid was adsorbed onto PMMA, PS, and AN69ST membranes, but only temporarily, and this did not affect drug bioavailability.

Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

“…The mechanism of cytokine adsorption by PMMA seems to involve hydrophobic binding, but this is not fully understood. Additionally, we confirmed that the adsorption capacity of cytokine-adsorbing hemofilters is sufficient for small amounts of substances, such as cytokines, but has no effect on antimicrobial agents, which are millions of times higher than the blood concentration of cytokines, because they exceed the saturation amount [114].…”

Comparison of myoglobin clearance in three types of blood purification modalities

“…Thus, it was presumed that it was removed in the filtrate beyond the adsorption limit [17]. This phenomenon may be supported by the fact that PMMA membranes show almost no adsorption properties for antibacterial agents [18]. Additionally, the principle of ion adsorption may not work on neutrally charged myoglobin (isoelectric point = 6.9) in the negatively charged AN69ST membrane.…”

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy

“…Doripenem is eliminated by the kidney. Doripenem was not absorbed onto AN69ST, polymethylmethacrylate, and polysulfone membranes (Hiraiwa et al, 2020). CVVHD could accelerate the elimination of doripenem (Tanoue et al, 2011).…”