Caspofungin sequestration in a polyacrylonitrile-derived filter: Increasing the dose does not mitigate sequestration

Abstract

Critically ill patients frequently require continuous renal replacement therapy. Echinocandins are recommended as first-line treatment of candidemia. Preliminary results suggested echinocandin sequestration in a polyacrylonitrile filter. The present study aimed at determining whether increasing the dose might balance sequestration. STX® filter, Baxter-Gambro was used. A liquid chromatography-mass spectrometry method was used for dosage of caspofungin. In vitro drug disposition was evaluated by NeckEpur® technology using a crystalloid medium instead of diluted/reconstituted blood, focusing on the disposition of the unbound fraction of drugs. Two concentrations were assessed. At the low dose, the mean measured initial concentration in the central compartment (CC) was 5.1 ± 0.6 mg/L. One hundred percent of the initial amount was eliminated from the CC within the 6-hour session. The mean total clearance from the CC was 9.6 ± 2.5 L/h. The mean percentages of elimination resulting from sequestration and diafiltration were 96.0 ± 5.0 and 4.0 ± 5.2%, respectively. At high dose, the mean measured initial concentration in the CC was 13.1 mg/L. One hundred percent of the initial amount was eliminated from the CC within the 6-hour session. The mean total clearance from the CC was 9.5 L/h. The mean percentages of elimination resulting from sequestration and filtration were 88.5 and 11.5%, respectively. Increasing the dose does not mitigate caspofungin sequestration in STX® filter. The results raise caution about the simultaneous use of caspofungin and polyacrylonitrile-derived filters. Intermittent modes of renal replacement therapy might be considered. For sensitive species, fluconazole might be an alternative.