Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption

Abstract Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventio...

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Autores principales:	Antoine G. Schneider, Pascal André, Joerg Scheier, Monika Schmidt, Heiko Ziervogel, Thierry Buclin, Detlef Kindgen-Milles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/baa4e73a6b9a4c3dad1d234ed5468cfc
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spelling	oai:doaj.org-article:baa4e73a6b9a4c3dad1d234ed5468cfc2021-12-02T14:58:45ZPharmacokinetics of anti-infective agents during CytoSorb hemoadsorption10.1038/s41598-021-89965-z2045-2322https://doaj.org/article/baa4e73a6b9a4c3dad1d234ed5468cfc2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89965-zhttps://doaj.org/toc/2045-2322Abstract Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r2 = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.Antoine G. SchneiderPascal AndréJoerg ScheierMonika SchmidtHeiko ZiervogelThierry BuclinDetlef Kindgen-MillesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antoine G. Schneider Pascal André Joerg Scheier Monika Schmidt Heiko Ziervogel Thierry Buclin Detlef Kindgen-Milles Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption
description	Abstract Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r2 = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.
format	article
author	Antoine G. Schneider Pascal André Joerg Scheier Monika Schmidt Heiko Ziervogel Thierry Buclin Detlef Kindgen-Milles
author_facet	Antoine G. Schneider Pascal André Joerg Scheier Monika Schmidt Heiko Ziervogel Thierry Buclin Detlef Kindgen-Milles
author_sort	Antoine G. Schneider
title	Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption
title_short	Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption
title_full	Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption
title_fullStr	Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption
title_full_unstemmed	Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption
title_sort	pharmacokinetics of anti-infective agents during cytosorb hemoadsorption
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/baa4e73a6b9a4c3dad1d234ed5468cfc
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Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption

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