Similarity between the in vitro activity and toxicity of two different Fungizone/Lipofundin admixtures.
OBJECTIVE
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 0.05 mg x 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 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.


CONCLUSIONS
The Fungizon-Lipofundin admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.
Araújo
Ivonete Batista
IB
Laboratory of Dispersed Systems (LASID), UFRN, Brazil.
Brito
C Ramon N
CR
Urbano
Isabel A
IA
Dominici
Victor A
VA
Silva Filho
Miguel A
MA
Silveira
Walteçá L L
WL
Damasceno
Bolívar P G L
BP
Medeiros
Aldo Cunha
AC
Egito
E Sócrates T
ES
D000666:Amphotericin B / Q000009:adverse effects / Q000494:pharmacology*; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000009:adverse effects / Q000494:pharmacology*; D041022:Candida tropicalis / Q000187:drug effects; D004337:Drug Carriers; D004338:Drug Combinations; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010288:Parenteral Nutrition / Q000592:standards*; D010743:Phospholipids / Q000009:adverse effects / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D013012:Sorbitol / Q000009:adverse effects / Q000494:pharmacology*; D016896:Treatment Outcome
D000935:Antifungal Agents; D004337:Drug Carriers; D004338:Drug Combinations; D006454:Hemoglobins; D010743:Phospholipids; C008288:Lipofundin; D013012:Sorbitol; D000666:Amphotericin B; D011188:Potassium