Amphotericin B/Emulsion Admixture Interactions: An Approach Concerning the Reduction of Amphotericin B Toxicity

Egito, Eryvaldo Sócrates Tabosa do; Araújo, Ivonete Batista de; Damasceno, Bolívar Ponciano Goulart de Lima; Price, James C.

doi:10.1002/jps.10223

Cited by 25 publications

(35 citation statements)

References 49 publications

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“…The data presented above (Figures 1 to 3) confirm the results that were published previously by our group 7,8 . They relate the influence of Fungizone TM / Lipofundin TM admixtures in decreasing RCB hemolysis.…”

Section: Discussionsupporting

confidence: 90%

“…However, additional studies should be addressed to this "new pharmaceutical entity" to clearly understand its mechanism of action. Recentrly we have developed some physicochemical studies on this AmB-lipid admixture system and showed, by spectrophotometric studies, that the presence of oligomeric AmB species is reduced in such preparation 7 .…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the effectiveness and toxicity of AmB, 4mL of RBC (5 x 10 7 cell/ml) or 2mL of Ct (5 x 10 7 cfu/ml) suspension were incubated by one hour at 37ºC with AmB-D, AmB-DL or AmB-DAL, respectively. Each experiment was accomplished in triplicate and repeated three times (7,13). The results were expressed in percentage of hemoglobin and K + leakage by the RBC and the percentage of K + release and CSR for Ct.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group has shown that the way in which FungizonÔ is incorporated into the emulsion (Intralipid ™ or Lipofundin ™ ) did not change the profile of activity or toxicity found for the AmB admixtures 7,8 . Therefore, the response against mammalian or fungal cells was remained.…”

Section: Introductionmentioning

confidence: 99%

“…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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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%