Abstract
Background: Cytokine hemoadsorption might be effective in patients with sepsis. However, its effect on anti-infective agents' pharmacokinetics remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. Methods: This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham procedure (controls) and to a drug combination (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 circulation) were performed within six hours of administration. Total clearance and adsorber-specific clearances were computed at each time point.Results: Hemoadsorption was associated with increased clearance of all study drugs, except for ganciclovir. Its impact on total body clearance was major for fluconazole (+282%), linezolid (+115%) and amphotericin B (+75%). It was minor for posaconazole (+32%), teicoplanin (+31%), anidulafungin (+23%), piperacillin (+19%), flucloxacillin (+16%), metronidazole (+16%) and ciprofloxacin (+15%) and insignificant (<10%) 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). Conclusions: Hemoadsorption with CytoSorb® has limited effect on the pharmacokinetics of most tested anti-infective drugs but appears to increase fluconazole, linezolid and liposomal amphotericin B clearance. Studies in humans with sepsis are required to confirm these findings.
01 / Myocardium protection against ischemic-reperfusion injury by nitric oxide supply to the extracorporeal circulation line during cardiopulmonary bypass (experimental study)
