Drug-Induced Nephrotoxicity Caused by Amphotericin B Lipid Complex and Liposomal Amphotericin B: A Review and Meta-Analysis

Immunology Research Program, Department of Infectious Diseases, Infection Control and Employee Health, The Anderson Cancer Center, Houston, Texas 77030, USA.
Medicine (Impact Factor: 5.72). 07/2010; 89(4):236-44. DOI: 10.1097/MD.0b013e3181e9441b
Source: PubMed


Lipid preparations of amphotericin B, commonly used to treat fungal infections, have been demonstrated to have reduced nephrotoxicity compared to conventional amphotericin B. However, to our knowledge, a comprehensive comparison of nephrotoxicity induced by different lipid preparations of amphotericin B has not been performed. We conducted a meta-analysis to evaluate nephrotoxicity associated with amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AmB). We searched the PubMed MEDLINE database and abstracts presented at key scientific meetings, and identified 11 studies reported between 1995 and 2008 that compared nephrotoxicity resulting from the use of these agents. Eight of the 11 studies were included in the meta-analysis. The Cochran-Mantel-Haenszel test was used to determine odds ratio (OR) and relative risk (RR), and the Breslow-Day test was used to analyze homogeneity of ORs across different studies. Analysis of all 8 studies (n = 1160) included in the meta-analysis showed an increased probability of nephrotoxicity in patients treated with ABLC versus L-AmB (OR, 1.75; RR, 1.55), but there was a significant lack of homogeneity across these studies (p < 0.001). After excluding the study by Wingard et al, the probability of experiencing nephrotoxicity was more similar between the 2 AmB lipid preparations (OR, 1.31; RR, 1.24; n = 916), particularly when the analysis included only the salvage patient population reported by Hachem et al (OR, 1.12; RR, 1.09; n = 839); the 7 remaining studies were more homogenous by Breslow-Day test (p = 0.054). Our results suggest that nephrotoxicity is generally similar for ABLC and L-AmB in patients receiving antifungal therapy and prophylaxis.

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    • "Amphotericin B is generally considered primary line of defence to tackle infections by Candida species and is often given in combination with more efficacious and less toxic systemic azole antifungal drugs such as fluconazole, miconazole, ketoconazole etc. However, amphotericin B overdose can be nephro and hepatotoxic (Safdar et al. 2010) and indiscriminate use of azole drug such as fluconazole can result in its intrinsic tolerance among C. albicans and non-albicans Candida species (Sanglard et al. 2003). Therefore, resistance to the azole antifungal drugs against Candida species has become predictable over a period of time which can be attributed to its fungistatic rather than the fungicidal nature in general (Vandenbosch et al. 2010). "
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    ABSTRACT: Patil S, Maknikar P, Wankhade S, Ukesh C, Rai M. 2015. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs. Nusantara Bioscience 7: 55-59. We report evaluation of antifungal activity of cumin seed oil and its pharmacological interactions when used in combination with some of the widely used conventional antifungal drugs using CLSI broth microdilution, agar disc diffusion and checkerboard microtitre assay against Candida. The essential oil was obtained from cumin seeds using hydrodistillation technique and was later evaluated for the presence of major chemical constituents present in it using gas chromatography and mass spectrometry (GC-MS) assay. The GC-MS assay revealed the abundance of γ-terpinene (35.42%) followed by p-cymene (30.72%). The agar disc diffusion assay demonstrated highly potent antifungal effect against Candida species. Moreover, the combination of cumin essential oil (CEO) with conventional antifungal drugs was found to reduce the individual MIC of antifungal drug suggesting the occurrence of synergistic interactions. Therefore, the therapy involving combinations of CEO and conventional antifungal drugs can be used for reducing the toxicity induced by antifungal drugs and at the same time enhancing their antifungal efficacy in controlling the infections caused due to Candida species.
    • "The results showed that the percentage of lycopene entrapment efficacy was 78.5% ± 2. Table 1 shows mean particle size, zeta-potential, and polydispersity index of empty and lycopene-loaded nanospheres. Size homogeneity of empty and loaded nanospheres suggested that lycopene was entrapped into nanoparticle core, according to previous studies.[2829] In this work, the results from vesicle size distribution showed a monomodal pattern. "
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    ABSTRACT: Background: Lycopene, a plant carotenoid, has potent effects against the various types of cancer cells. To date, the effect of lycopene in the free and encapsulated forms on the telomerase activity in human leukemia cell line K562 have not been investigated. The aim of the present study was to prepare a novel lycopene-loaded nanosphere and compare its anti-telomearse activity in K562 cell line with those of free lycopene. Materials and Methods: The lycopene-loaded nanospheres were prepared by nanoprecipitation method. The lycopene entrapment efficacy was measured by high-performance liquid chromatography (HPLC) method. The anti-proliferation effect of the lycopene in the free and encapsulated forms in the different times (0-72 h) and the different doses (0-100 μg/ml) on K562 cell line was studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The changes of telomerase activity, following treatment with the lycopene in the free and encapsulated forms, were detected using the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay. Results: The entrapment efficacy of lycopene was 78.5% ± 2. Treatment of the K562 cell line with lycopene, in particular in encapsulated form, resulted in a significant inhibition of the cell growth and increasing of percentage of apoptotic cells. It has also been observed that the telomerase activity in the lycopene-loaded nanospheres-treated cells was significantly inhibited in a dose and time-dependent manner. Conclusion: Our data suggest a novel mechanism in the anti-cancer activity of the lycopene, in particular in encapsulated form, and could be provided a basis for the future development of anti-telomerase therapies.
    Pharmacognosy Magazine 03/2014; 10(Suppl 1):S157-63. DOI:10.4103/0973-1296.127368 · 1.26 Impact Factor
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    • "One of the major limitations associated with AmpB is its nephrotoxicity [12]. Another issue related to AmpB is its poor solubility that limits its route of administration [13]. "
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    ABSTRACT: Invasive fungal infections such as candidiasis constitute an increasingly important medical problem. Drugs currently used for the treatment of candidiasis include polyenes (such as Amphotericin B) and azoles. Amphotericin B (AmpB) presents several limitations such as its nephrotoxicity and limited solubility. We have developed two novel lipid-based AmpB formulations which in vivo show less nephrotoxicity and enhanced solubility compared to Fungizone™ a commercial AmpB formulation. The purpose of this study was to determine the cytotoxicity of Fungizone™, Ambisome™ and two novel AmpB formulations (iCo-009 and iCo-010) against Candida albicans, human kidney (293T) cells and monocytic (THP1) cells. Cell cytotoxicity to the AmpB formulations was evaluated by MTS and LDH assays. In vitro anti-Candida albicans activity was assessed after a 48 h drug incubation. None of the AmpB formulations tested showed cytotoxicity against 293T cells. In the case of THP1 cells only Fungizone™ and Ambisome™ showed cytotoxicity at 500 μg/L (n = 4-10, p < 0.05).The calculated EC50 to Candida albicans for the different formulations was as follows: 26.8 ± 2.9 for iCo-010, 74.6 ± 8.9 for iCo-009, 109 ± 31 for Ambisome™ and 87.1 ± 22 for Fungizone™ (μg of AmpB/L, n = 6-12, p < 0.05). The AmpB formulations analyzed were not cytotoxic to 293T cells. Cytotoxicity in THP1 cells was observed for Fungizone™ and Ambisome™, but not with the novel AmpB formulations. iCo-010 had higher efficacy compared to other three AmpB formulations in the Candida albicans model.The absence of cytotoxicity as well as its higher efficacy for the Candida model compared to Fungizone™ and Ambisome™ suggest that iCo-010 has potential in treating candidiasis.
    Lipids in Health and Disease 08/2011; 10(1):144. DOI:10.1186/1476-511X-10-144 · 2.22 Impact Factor
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