Is preloading with amikacin a measure able to mitigate sequestration? A preliminary in vitro study.

Abstract

Introduction: Amikacin is sequestered in polyacrylonitrile filters. Methods mitigating sequestration are unknown. Amikacin elimination in a polyacrylonitrile-derived filter preloaded with amikacin was studied in a preliminary study.

Methods: Amikacin concentrations were determined using an immunochemical method. Prismaflex™, Baxter-Gambro, and the ST™150 filter were used. Sessions were performed in a continuous diafiltration mode. Diafiltration flow rate was set to 2500 mL/h and filtration to 500 mL/h pre- and 1000 mL/h post-dilution. Net loss was set to zero. In sessions with preload, a 150 mg dose of amikacin was injected in the first 1 L bag of physiological saline when starting the priming. NeckEpur^® method was used for pharmacokinetic calculations.

Results: In the central compartment (CC), the mean initial concentration in the sessions without and with preload was 81.8 ± 6.0 mg/L. There were no significant differences in the AUC_cc and AUC_inlet without or with preload. The preloading dose induced a significant increase in the AUC_outlet. Compared with sessions without preload, the clearance from the CC in sessions with preload decreased from 4.94 ± 0.43 to 3.75 ± 0.32 L/h, respectively. The elimination rates by diafiltration and sequestration in the sessions without and with preload were 82.3 ± 6.2/17.8 ± 6.2% and 125 ± 9.2%/0 ± 0%, respectively. The 150 mg loading dose was eliminated by diafiltration (42.5%) and by sequestration (57.5%).

Conclusion: Preloading filter with amikacin modifies the disposition of amikacin by preventing further sequestration. Studies are needed to define an efficient preloading dosage regimen in actual condition of use.