Kinetics of Linezolid in Continuous Renal Replacement Therapy: An In Vitro Study

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Abstract

Background:

Continuous veno-venous hemofiltration (CVVH) could affect the pharmacokinetic profile of linezolid (LZD). The aim of this study was to evaluate the LZD extracorporeal clearance using an in vitro CVVH model.

Methods:

A sham miniaturized CVVH circuit (CARPEDIEM; Bellco, Mirandola, Italy) was set up with a polysulfone hemofilter (0.25 m2; cutoff 50,000 Da) for 240 minutes using normal saline solution (0.9% wt/vol NaCl) and blood (n = 6) spiked with LZD. Drug solution samples were collected during CVVH at 10, 30, 60, 120, and 240 minutes. LZD levels were measured by high-performance liquid chromatography.

Results:

Results were used to estimate pharmacokinetic parameters. The LZD baseline level decreased from 17.24 ± 0.54 to 9.73 ± 4.85 mg/L and from 11.75 ± 0.08 to 5.01 ± 0.67 mg/L in the first 10 minutes, and then increased to 13.2 ± 3.10 and 7.4 ± 0.71 mg/L in normal saline solution and blood, respectively. Mass balance analysis reported a rapid adsorption of LZD onto a polysulfone membrane followed by its release: a rebound phenomenon occurred.

Conclusions:

Although further studies are necessary to clarify this phenomenon, LZD level variations observed in our study should be considered to avoid antimicrobial underexposure. Several strategies are available for adjusting the dosage regimen of LZD, but therapeutic drug monitoring is highly recommended when it is used.

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