Influence of Albumin Dialysis on Pharmacokinetics of Amphotericin B Colloidal Dispersion and Amphotericin B Lipid Complex

Weiler, Stefan; Vogelsinger, Helene; Joannidis, Michael; Dunzendorfer, Stefan; Bellmann, Romuald

doi:10.1111/j.1525-1594.2010.01111.x

Cited by 13 publications

(7 citation statements)

References 20 publications

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“…In three patients treated with albumin dialysis for cholestatic liver failure who received lipid-formulated amphotericin B (one patient liposomal amphotericin B, one amphotericin B colloidal dispersion and one patient amphotericin B lipid complex), exposure with liberated amphotericin B was slightly decreased. However, a dose adjustment of lipid-formulated amphotericin B for albumin dialysis is probably not necessary [ 62 , 63 ]. In a patient on extracorporeal membrane oxygenation (ECMO), amphotericin B levels were measured 13 and 18 h after administration of liposomal amphotericin B at a dose of 3 mg/kg.…”

Section: Amphotericin Bmentioning

confidence: 99%

Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients

2017

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IntroductionBecause of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety.Materials and methodsThis review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy.Conclusions and discussionAmphotericin B is eliminated unchanged via urine and faeces. Flucytosine and fluconazole display low protein binding and are eliminated by the kidney. Itraconazole, voriconazole, posaconazole and isavuconazole are metabolised in the liver. Azoles are substrates and inhibitors of cytochrome P450 (CYP) isoenzymes and are therefore involved in numerous drug–drug interactions. Anidulafungin is spontaneously degraded in the plasma. Caspofungin and micafungin undergo enzymatic metabolism in the liver, which is independent of CYP. Although several drug–drug interactions occur during caspofungin and micafungin treatment, echinocandins display a lower potential for drug–drug interactions. Flucytosine and azoles penetrate into most of relevant tissues. Amphotericin B accumulates in the liver and in the spleen. Its concentrations in lung and kidney are intermediate and relatively low myocardium and brain. Tissue distribution of echinocandins is similar to that of amphotericin. Combination antifungal therapy is established for cryptococcosis but controversial in other IFIs such as invasive aspergillosis and mucormycosis.

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Section: Amphotericin Bmentioning

confidence: 99%

Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients

2017

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“…Only two reports regarding the use of antifungals during AD were found in the literature, demonstrating that the influence of this technique on drug elimination appeared to be negligible [3,4]. We report the first pharmacokinetic study of anidulafungin during AD.…”

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Pharmacokinetics of anidulafungin during albumin dialysis

et al. 2014

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“…Extracorporeal albumin dialysis can be applied to support the hepatic detoxification of protein-bound substrates in severe CSLD. Recently, we observed that the elimination of the colloidal AMB fraction was markedly accelerated by albumin dialysis whereas the clearance of liberated AMB was only moderately enhanced by this technique (24).…”

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Pharmacokinetics of Amphotericin B Colloidal Dispersion in Critically Ill Patients with Cholestatic Liver Disease

Weiler

Überlacher²,

Schöfmann³

et al. 2012

Antimicrob Agents Chemother

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The pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD. Liver disease has been identified as a risk factor for invasive fungal infections (IFIs) such as invasive aspergillosis in critically ill patients (15,16). Amphotericin B (AMB) has a broad antimycotic spectrum and is therefore a cornerstone in the treatment of IFIs. Because of its renal toxicity, however, conventional AMB is frequently replaced by less toxic lipid formulations such as AMB colloidal dispersion (ABCD; Amphocil, Amphotec). ABCD contains AMB as a cholesteryl sulfate complex forming disc-like structures of 74 to 170 nm in diameter (5). AMB does not undergo hepatic metabolism, but it is eliminated in part via the bile. ABCD is rapidly taken up by liver macrophages (11,25). Clinical studies on the influence of hepatic impairment on AMB pharmacokinetics are lacking so far. Therefore, the pharmacokinetics of lipidbound (colloidal) AMB and of AMB liberated from its lipid binding was assessed under single-dose and steady-state conditions in critically ill patients with and without cholestatic liver disease (CSLD) treated with ABCD.The study was approved by the local ethics committee. Time-AMB concentration profiles were determined in critically ill patients with CSLD (defined as plasma bilirubin of Ͼ10 mg/dl due to CSLD) and in a control group comprising critically ill patients with approximately normal hepatic function (bilirubin of Ͻ1.28 mg/dl). Patients with a plasma bilirubin level between 1.28 and 10 mg/dl and patients with a plasma bilirubin level of Ͼ10 mg/dl caused by disorders other than CSLD (e.g., hemolysis) were excluded from the study. ABCD was administered for suspected or proven IFIs over 4 h at a dose of ϳ4 mg/kg of body weight. In order to avoid infusion-related toxicity, ϳ2 mg/kg was given on day 1. In all patients enrolled, conventional AMB deoxycholate was contraindicated because of its renal toxicity. Blood samples of 2 ml were taken from an arterial line on day 1 of ABCD therapy (single dose) and on day 5 or later (steady state) before ABCD administration as well as 4,6,8,12, and 24 h after the start of infusion. Lipid-bound (colloidal) AMB and AMB that had been liberated from its lipid binding in the plasma were separated by solid-phase extraction and quantified by high-performance liquid chromatography as described previously (10). The pharmacokinetics of lipid-bound, liberated, and total AMB was calculated by Kinetica 2000 (InnaPhase Corporation, Champs-sur-Marne, France) using a noncompartmental model. The area under the concentration-time curve from time zero to 24 h (AUC 0 -24...

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Influence of Albumin Dialysis on Pharmacokinetics of Amphotericin B Colloidal Dispersion and Amphotericin B Lipid Complex

Cited by 13 publications

References 20 publications

Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients

Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients

Pharmacokinetics of anidulafungin during albumin dialysis

Pharmacokinetics of Amphotericin B Colloidal Dispersion in Critically Ill Patients with Cholestatic Liver Disease

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