Pharmacokinetics of Liposomal Amphotericin B During Extracorporeal Albumin Dialysis

Vogelsinger, Helene; Joannidis, Michael; Kountchev, Jordan; Bellmann‐Weiler, Rosa; Wiedermann, Christian J.; Bellmann, Romuald

doi:10.1111/j.1525-1594.2006.00192.x

Cited by 11 publications

(12 citation statements)

References 12 publications

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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.…”

mentioning

confidence: 94%

Pharmacokinetics of anidulafungin during albumin dialysis

et al. 2014

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confidence: 94%

Pharmacokinetics of anidulafungin during albumin dialysis

et al. 2014

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“…Thus, only small amounts of AMB, probably the liberated component, appear to be excreted via the bile during treatment with LAMB or ABCD. By contrast, in liver tissue, AMB concentrations of ~ 100 µg/g were measured, probably because of accumulation in reticuloendothelial cells [20]. demonstrated by microcalorimetry.…”

Section: Discussionmentioning

confidence: 84%

Biliary amphotericin B pharmacokinetics and pharmacodynamics in critically ill liver transplant recipients receiving treatment with amphotericin B lipid formulations

Welte¹,

Eschertzhuber²,

Weiler³

et al. 2015

International Journal of Antimicrobial Agents

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Fungal cholangitis is a potentially life-threatening condition. As amphotericin B (AmB) has a broad antimycotic spectrum, in this study its biliary penetration and activity was determined in two patients treated with liposomal AmB (L-AmB) and in one patient receiving AmB colloidal dispersion (ABCD). Biliary and plasma AmB levels were quantified by high-performance liquid chromatography after purification by solid-phase extraction. For assessment of biliary AmB activity, isolates of Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were incubated in porcine bile at AmB concentrations of 0.025-5.00 mg/L. In addition, patient bile samples retrieved for AmB quantification were inoculated with the same Candida strains. Biliary AmB concentrations were lower and displayed a slower rise and decline than plasma levels. The highest penetration ratio, as expressed by the ratio between the area under the AmB concentration-time curve in bile and plasma (liberated AmB) over the sampling period (AUC0-n bile/AUC0-n LI plasma), was 0.28. Proliferation of C. albicans and C. tropicalis in bile was similar to that in culture medium, whereas growth of C. glabrata was diminished and proliferation of C. krusei was absent in bile. In comparison with culture medium, AmB activity decreased in spiked porcine bile. In all but one patient bile sample, fungal growth was delayed or lacking even when AmB was not detectable. However, no fungicidal effect was observed in patient bile at AmB concentrations up to 1.28 mg/L. Thus, a reliable response of fungal cholangitis to treatment with L-AmB or ABCD cannot be anticipated. Biliary AMB concentrations were lower and displayed a slower rise and decline than plasma levels. The highest penetration ratio as expressed by the ratio between the area under the time-AMB-concentration curve in bile and plasma (liberated AMB) over the sampling period (AUC 0-n bile /AUC 0-n LI plasma ) amounted to 0.28. Proliferation of C. albicans and C. tropicalis in bile was similar to that in culture medium whereas growth of C. glabrata was diminished and proliferation of C. krusei was absent in bile. In comparison with medium, AMB activity decreased in spiked porcine bile. In all but one patient bile sample, fungal growth was delayed or lacking, even when AMB was not detectable. However, no fungicidal effect was observed in patient bile at AMB concentrations of up to 1.28 mg/L. Thus, a reliable response of fungal cholangitis to treatment with LAMB or ABCD cannot be anticipated.

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“…Previously, similar levels of liberated AMB and much higher concentrations of lipid-associated AMB were measured during LAMB treatment and AD (9).…”

Section: Resultsmentioning

confidence: 99%

“…Pharmacokinetic data on antimicrobial agents-in particular on antimycotics-administered under AD are very sparse (8,9). AMB lipid preparations are clinically used for the treatment of invasive fungal infections in patients with a high risk of renal toxicity.…”

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confidence: 99%

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

et al. 2011

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Albumin dialysis (AD) is a therapeutic option in severe cholestatic liver failure. However, it can significantly enhance drug elimination. Pharmacokinetic data on antimicrobial agents--in particular on antimycotics--administered under this clinical condition are very sparse. Therefore, amphotericin B (AMB) plasma concentrations were measured in two critically ill patients who were treated with AD because of severe cholestatic liver failure and were prescribed lipid formulated AMB--either AMB colloidal dispersion (ABCD) or AMB lipid complex (ABLC)--for suspected invasive fungal infection. AD was performed with the molecular adsorbent recirculating system (MARS). Lipid-associated and liberated AMB were separately quantified on and off AD. The clearance of the liberated AMB fraction was not essentially affected (ABLC) or moderately enhanced during AD by a factor of 2.5 (ABCD). The clearance of the lipid-formulated fraction was increased by a factor of 4 during AD (ABCD) or was similar (ABLC) on and off AD. Despite the fact that there was a four-fold higher clearance of the lipid-formulated fraction of ABCD, the clinically relevant area under the concentration time curve of the liberated AMB fraction was only moderately changed (by 37% in ABCD, 70% in ABLC) during AD. Thus, the effect of AD on lipid formulated AMB appears to be moderate. A daily dose of 5 mg/kg will probably lead to adequate plasma levels in patients on AD.

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Pharmacokinetics of Liposomal Amphotericin B During Extracorporeal Albumin Dialysis

Cited by 11 publications

References 12 publications

Pharmacokinetics of anidulafungin during albumin dialysis

Pharmacokinetics of anidulafungin during albumin dialysis

Biliary amphotericin B pharmacokinetics and pharmacodynamics in critically ill liver transplant recipients receiving treatment with amphotericin B lipid formulations

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

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