Determination of the Relative Toxicity of Amphotericin B Formulations: A Red Blood Cell Potassium Release Assay

Jensen, Greg; Skenes, Craig; Bunch, T. H.; Weissman, C. A.; Amirghahari, N.; Satorius, A.; Moynihan, Karen; Eley, Crispin G. S.

doi:10.1080/107175499266995

Cited by 41 publications

(47 citation statements)

References 21 publications

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“…, AmB-DAL and AmB-DL were discreetly less effective showing a small number of CFU ( Figure 3) not statistically significant, at 50 mg.L - 1 .…”

Section: Resultsmentioning

confidence: 99%

“…An alternative could be a new delivery system based on the lipid emulsions used for parenteral nutrition in clinical practice (Intralipid ™ or Lipofundin ™ ). This system has been showing to reduce the AmB toxicity with little damage in its efficacy 1 . In fact, the reduction of the toxicity of FungizonÔ -IntralipidÔ admixtures was observed in several clinical trials 1,6 .…”

Section: Introductionmentioning

confidence: 99%

“…This system has been showing to reduce the AmB toxicity with little damage in its efficacy 1 . In fact, the reduction of the toxicity of FungizonÔ -IntralipidÔ admixtures was observed in several clinical trials 1,6 . In 2002, an in vitro evaluation of FungizonÔ and FungizonÔ/ Lipofundinä admixture revealed that the latter one was less toxic against red blood cells, presenting no hemolytic activity 7 .…”

Section: Introductionmentioning

confidence: 99%

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Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

et al. 2005

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Araújo IB, Brito CRN, Urbano IA, Dominici VA, Silva-Filho MA, Silveira WLL, Damasceno BPGL, Medeiros AC, Egito EST. Similarity between the in vitro activity and toxicity of two different fungizoneä / lipofundinä admixtures. Acta Cir Bras [serial on line] Available from: URL: htt://www.scielo.br/acb.ABSTRACT -Purpose: Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K + leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L -1 ). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L -1 , although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™-Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.

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“…, AmB-DAL and AmB-DL were discreetly less effective showing a small number of CFU ( Figure 3) not statistically significant, at 50 mg.L - 1 .…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

et al. 2005

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“…Esta lesión, medida en ensayos de hemólisis in vitro, es más frecuente con la formulación de dispersión coloidal, seguida de aquella en complejo lipídico. Se requieren concentraciones 1.000 veces mayores de AmB liposomal para producir el mismo nivel de daño celular 18 . También puede producir cardiotoxicidad con dosis superiores al rango terapéutico, que se manifiesta como arritmias ventriculares y bradicardia, lo cual se ha observado incluso con AmB liposomal 19,20 .…”

Section: Toxicidad Agudaunclassified

Formas lipídicas de anfotericina

Botero

Puentes-Herrera

Cortés

2014

Rev. chil. infectol.

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“…Le caratteristiche farmaceutiche, farmacocinetiche, farmacodinamiche e terapeutiche delle tre formulazioni lipidiche di amfotericina B differiscono sensibilmente tra loro e non possono essere ritenute intercambiabili [14][15][16][17][18][19][20].…”

Section: Introduzioneunclassified

Analisi Costo-Efficacia di Amfotericina B Liposomiale (L-AmB) versus Amfotericina B Complesso Lipidico (ABLC) nel trattamento empirico della neutropenia febbrile

Eandi

2005

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Current international guidelines for the management of immuno-compromised patients with febrile neutropenia recommend a systemic antimicrobial therapy if fever hasn't receded after three days of antibiotic treatment. Amphotericin B remains the gold standard because of its broad spectrum fungicidal action and minimal resistance development risk. Nonetheless, therapeutic use of the standard formulation, Amphotericin B deoxycholate, is limited by its toxicity, especially on the kidneys. To counteract this, amphotericin B has been encapsulated in liposomes, a process which reduces its toxicity and allows higher doses to be given. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (L-AmB). These lipid formulations differ in pharmacodynamics and pharmacokinetics, and can't therefore be considered interchangeable. Besides, they are more expensive than Amphotericin B deoxycholate. Aim of the study is to perform a cost/effectiveness analysis (CEA) comparing L-AmB (3mg/kg/die or 5mg/kg/ die) and ABLC (5mg/kg/die) as first-line antimicrobial empirical treatments in immuno-compromised patients with febrile neutropenia resistant to broad spectrum antibiotics. Secondly, we present a cost-minimization analysis (CMA) of the considered alternatives, assuming the same efficacy for all treatments. At the end we value the principal cost items from the point of view of the Italian Health Service, with a particular focus on the economic burden caused by adverse reactions. REVIEW § Ordinario di Farmacologia Clinica, Università degli Studi di Torino INTRODUZIONELe attuali linee guida di gestione dei pazienti immmunodepressi in stato di neutropenia febbrile prevedono venga instaurata una terapia antimicotica sistemica nel caso in cui la febbre non regredisca dopo 3 giorni di terapia antibiotica [1][2][3][4].Infatti, nei pazienti neutropenici sono relativamente frequenti le infezioni o le co-infezioni micotiche invasive sostenute da Candida e da Aspergillus. Entrambe queste micosi sistemiche sono difficili da diagnosticare nei soggetti immunocompromessi, soprattutto nelle primi fasi dell'infezione, poiché le loro manifestazioni cliniche sono spesso scarsamente differenziabili da altri tipi di infezioni o da altre manifestazioni patologiche come le polmoniti da raggi e la GVHD [5][6][7].L'amfotericina B, per la sua elevata attività antimicotica nei confronti sia di Candida che di Aspergillus, è tuttora considerata il trattamento di riferimento per i pazienti con neutropenia febbrile che non rispondono alla terapia antibiotica ad ampio spettro. Tuttavia la sua formulazione tradizionale (amfotericina B desossicolato) presenta un profilo rischiobeneficio non molto favorevole a causa della elevata tossicità sistemica, principalmente renale, che ne limita l'uso a dosi subottimali che non consentono di ottenere il massimo beneficio terapeutico dalla molecola [8,9].Nel tentativo di superare questa difficoltà e migliorare l'ind...

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Determination of the Relative Toxicity of Amphotericin B Formulations: A Red Blood Cell Potassium Release Assay

Cited by 41 publications

References 21 publications

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Formas lipídicas de anfotericina

Analisi Costo-Efficacia di Amfotericina B Liposomiale (L-AmB) versus Amfotericina B Complesso Lipidico (ABLC) nel trattamento empirico della neutropenia febbrile

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