Comparison of conventional and lipid emulsion formulations of amphotericin B: Pharmacokinetics and toxicokinetics in dogs

Nieto, Javier; Alvar, Jorge; Rodríguez, C.; Andrés, M. I. San; Andrés, M. D. San; González, F.

doi:10.1016/j.rvsc.2017.12.005

Cited by 10 publications

(9 citation statements)

References 42 publications

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“…Improved tolerance may be due to decreased expression of pro-inflammatory cytokines TNF-α and IL-1β found in mice with invasive fungal infections treated with AmB-IL when compared with dextrose infusions of AmB-DOC [134]. In preclinical and clinical studies, the AmB-IL admixture showed a different pharmacokinetic profile, with higher plasma clearance and higher steady-state volume of distribution (Table 1), and reduced adverse events compared to the standard AmB-DOC infusion in 5% dextrose [98,[136][137][138]. A recent systematic review and network meta-analysis of 25 randomized controlled trials (RCTs) enrolling a total of 2996 patients, aiming to evaluate the efficacy and safety of conventional AmB and lipid formulations, identified AmB-IL as the safest cost-saving treatment [139].…”

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confidence: 99%

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

2020

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Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated with deoxycholate as a micellar suspension for intravenous administration, but severe infusion-related side effects and nephrotoxicity hamper its therapeutic potential. Lipid-based formulations, such as liposomal AmB, have been developed which significantly reduce the toxic side effects of the drug. However, their high cost and the need for parenteral administration limit their widespread use. Therefore, delivery systems that can retain or even enhance antimicrobial efficacy while simultaneously reducing AmB adverse events are an active area of research. Among those, lipid systems have been extensively investigated due to the high affinity of AmB for binding lipids. The development of a safe and cost-effective oral formulation able to improve drug accessibility would be a major breakthrough, and several lipid systems for the oral delivery of AmB are currently under development. This review summarizes recent advances in lipid-based systems for targeted delivery of AmB focusing on non-parenteral nanoparticulate formulations mainly investigated over the last five years and highlighting those that are currently in clinical trials.

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confidence: 99%

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

2020

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“…3 Adverse effects associated with AmB parenteral administration include infusion reactions and more delayed effects, such as nephrotoxicosis. 4 There are several formulations of AmB, each with unique pharmacokinetic and toxicokinetic properties. Conventional AmB is complexed with sodium deoxycholate (AmB-D; Fungizone, Xediton Pharmaceuticals Inc., Ontario, CA).…”

Section: Introductionmentioning

confidence: 99%

Incidence of acute kidney injury in dogs with systemic mycotic infections treated with amphotericin B (1996‐2020)

Chan

Dear

Palm

et al. 2023

Veterinary Internal Medicne

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Background Amphotericin‐B (AmB) is an essential medication for the treatment of life‐threatening systemic mycoses but the incidence and risk factors for acute kidney injury (AKI) after its administration are not known in dogs. Objective Determine the incidence of and risk factors for AKI in dogs receiving AmB. Animals Fifty‐one client owned dogs receiving AmB for the treatment of systemic mycoses. Methods Retrospective study. Signalment, potential risk factors, AKI development (creatinine ≥0.3 mg/dL from baseline), drug formulation (deoxycholate [AmB‐D] or lipid complex [ABLC]), dose, and treatment duration were recorded. The probability of an AKI diagnosis was evaluated using a log‐rank test. The incidence of AKI and odds ratios were calculated for potential risk factors. Results Incidence of AKI was 5/12 (42%) for dogs receiving AmB‐D and 14/39 (36%) for dogs receiving ABLC. Of the 19 dogs that developed AKI, 16 (84%) continued treatment after a pause in the planned dosing protocol. Fifty percent of dogs received a cumulative dose of 6.9 mg/kg for AmB‐D and 22.5 mg/kg for ABLC (P < .01) at time of AKI diagnosis. ICU hospitalization (odds ratio [OR] 0.21, 95% confidence interval [CI]: 0.58‐0.87) and inpatient status (OR 0.25, 95% CI: 0.07‐0.86) were associated with decreased odds of AKI. Conclusions and Clinical Importance Incidence of AKI with AmB is common but does not always preclude continued treatment. The incidence of AKI is similar between AmB‐D and ABLC, but dogs receiving ABLC tolerated a higher cumulative total dose before AKI diagnosis.

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“…However, C. albicans in the biofilm shows high resistance to AMB, which can be 1,000-fold less susceptible than planktonic ones. Several lipid-based drug delivery systems have been employed to enhance the therapeutic effect and decrease the toxicity of AMB ( Weiler et al, 2008 ; Nieto et al, 2018 ). Unfortunately, the widespread use of these new formulations is impeded due to the high production cost ( Weiler et al, 2009 ; Steimbach et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Antibiofilm Activity of β-1,3-Glucanase-Functionalized Nanoparticles Loaded With Amphotericin B Against Candida albicans Biofilm

Tan

Ding

et al. 2022

Front. Microbiol.

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Candida biofilm-related infections cause increased morbidity and mortality in patients with a reduced immune response. Traditional antifungal therapies have proven to be insufficient as the biofilm matrix acts as a perfusion barrier. Thus, novel methods are required to improve drug delivery and kill Candida within the biofilm. In this study, chitosan nanoparticles (CSNPs) loaded with Amphotericin B (AMB), which were functionalized with β-1,3-glucanase (Gls), were fabricated (CSNPs-AMB-Gls), and their antibiofilm activity against Candida albicans biofilm was evaluated in vitro. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were employed to examine biofilm architecture and cell viability. CSNPs-AMB-Gls inhibited planktonic cell growth and biofilm formation effectively and exhibited the highest efficacy on the removal of a mature biofilm than free AMB or CSNPs-AMB. The created nanoparticles (NPs) were found to penetrate the biofilm so as to directly interfere with the cells inside and disassemble the biofilm matrix. CSNPs-AMB-Gls could also eradicate biofilms from clinical isolates. These results suggest the potential applicability of CSNPs-AMB-Gls for the treatment of Candida biofilm-related infections.

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Comparison of conventional and lipid emulsion formulations of amphotericin B: Pharmacokinetics and toxicokinetics in dogs

Cited by 10 publications

References 42 publications

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

Incidence of acute kidney injury in dogs with systemic mycotic infections treated with amphotericin B (1996‐2020)

Enhancing the Antibiofilm Activity of β-1,3-Glucanase-Functionalized Nanoparticles Loaded With Amphotericin B Against Candida albicans Biofilm

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