4.2 Article

Elimination of fluconazole during continuous renal replacement therapy. An in vitro assessment

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INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
卷 44, 期 7, 页码 453-464

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SAGE PUBLICATIONS LTD
DOI: 10.1177/0391398820976144

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Fluconazole; renal replacement therapy; filtration; adsorption; pharmacokinetics; alternative to animal testing

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The study using the NeckEpur® model found that neither the ST150®-polyacrylonitrile nor the AV1000®-polysulfone filters result in any significant adsorption of fluconazole during continuous renal replacement therapy.
Introduction: Continuous renal replacement therapy (CRRT) efficiently eliminates fluconazole. However, the routes of elimination were not clarified. Adsorption of fluconazole by filters is a pending question. We studied the elimination of fluconazole in a model mimicking a session of CRRT in humans using the NeckEpur(R) model. Two filters were studied. Methods: The AV1000(R)-polysulfone filter with the Multifiltrate Pro. Fresenius and the ST150(R)-polyacrylonitrile filter with the Prismaflex. Baxter-Gambro were studied. Continuous filtration used a flowrate of 2.5 L/h in post-dilution only. Session were made in duplicate. Routes of elimination were assessed using the NeckEpur(R) model. Results: The mean measured initial fluconazole concentration (mean +/- SD) for the four sessions in the central compartment (CC) was 14.9 +/- 0.2 mg/L. The amount eliminated from the CC at the end of 6 h-session at a 2.5 L/h filtration flowrate for the AV1000(R)-polysulfone and the ST150(R)-polyacrylonitrile filters were 90%-93% and 96%-94%, respectively; the clearances from the central compartment (CC) were 2.5-2.6 and 2.4-2.3 L/h, respectively. The means of the instantaneous sieving coefficient were 0.94%-0.91% and 0.99%-0.91%, respectively. The percentages of the amount eliminated from the CC by filtration/adsorption were 100/0%-95/5% and 100/0%-100/0%, respectively. Conclusion: Neither the ST150(R)-polyacrylonitrile nor the AV1000(R)-polysulfone filters result in any significant adsorption of fluconazole.

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