Araújo Ivonete Batista, Brito C Ramon N, Urbano Isabel A, Dominici Victor A, Silva Filho Miguel A, Silveira Walteçá L L, Damasceno Bolívar P G L, Medeiros Aldo Cunha, Egito E Sócrates T
Laboratory of Dispersed Systems (LASID), UFRN, Brazil.
Acta Cir Bras. 2005;20 Suppl 1:257-61.
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.
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 0.05 mg x L(-1)).
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 x 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.
The Fungizon-Lipofundin admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.
两性霉素B（AmB）是一种具有广谱活性的抗真菌药物，仍然是抗真菌治疗的金标准。然而，有时其高毒性使其无法用于临床。本研究的目的是评估和比较Fungizon（AmB-D）和两种新型不同AmB制剂的体外疗效和毒性。
研究了三种产品：Fungizon和两种Fungizon/Lipofundin混合物，通过两种方法进行稀释：第一种方法是先将Fungizon用注射用水稀释，然后加入Lipofundin（AmB-DAL）；第二种方法是将AmB-D作为粉末在所述乳剂中进行初步稀释（AmB-DL）。体外试验使用了两种细胞模型：来自人类供体的红细胞（RBC）和热带假丝酵母菌（Ct）。在四种AmB浓度（50至0.05mg x L(-1)）下进行体外评估（钾离子泄漏、血红蛋白泄漏和细胞存活率-CSR）。
结果表明，AmB的作用不仅取决于浓度，还取决于细胞类型和载体种类。在AmB浓度为50mg x L(-1)时，虽然AmB-D的血红蛋白泄漏几乎完全（99.51），但AmB-DAL和AmB-DL的该值趋于零。p = 0.000表明AmB-D的溶血作用明显更强。
Fungizon-Lipofundin混合物似乎是更有价值的AmB载体系统，因为它们具有最佳的治疗指数。
