Comparison of antifungal activity of amphotericin B deoxycholate suspension with that of amphotericin B cholesteryl sulfate colloidal dispersion.

ABSTRACT We investigated the compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to seven noninfected, catheterized rabbits received 1 mg of amphotericin B deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung tissue were obtained. Pharmacokinetic parameters in plasma were derived by model-independent techniques, and concentrations in ELF and PAM were calculated based on the urea dilution method and macrophage cell volume, respectively. Mean amphotericin B concentrations ± standard deviations (SD) in lung tissue and PAM were highest in ABLC-treated animals, exceeding concurrent plasma levels by 70- and 375-fold, respectively (in lung tissue, 16.24 ± 1.62 versus 2.71 ± 1.22, 6.29 ± 1.17, and 6.32 ± 0.57 μg/g for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0029]; in PAM, 89.1 ± 37.0 versus 8.92 ± 2.89, 5.43 ± 1.75, and 7.52 ± 2.50 μg/ml for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0246]). By comparison, drug concentrations in ELF were much lower than those achieved in lung tissue and PAM. Among the different cohorts, the highest ELF concentrations were found in LAMB-treated animals (2.28 ± 1.43 versus 0.44 ± 0.13, 0.68 ± 0.27, and 0.90 ± 0.28 μg/ml in DAMB-, ABCD-, and ABLC-treated animals, respectively [P = 0.0070]). In conclusion, amphotericin B and its lipid formulations displayed strikingly different patterns of disposition in lungs 24 h after dosing. Whereas the disposition of ABCD was overall not fundamentally different from that of DAMB, ABLC showed prominent accumulation in lung tissue and PAM, while LAMB achieved the highest concentrations in ELF.

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Pretreatment with Empty Liposomes Attenuates the Immunopathology of Invasive Pulmonary Aspergillosis in Corticosteroid-Immunosuppressed Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01268-06 ◽

2006 ◽

Vol 51 (3) ◽

pp. 1078-1081 ◽

Cited By ~ 33

Author(s):

Russell E. Lewis ◽

Georgios Chamilos ◽

Randall A. Prince ◽

Dimitrios P. Kontoyiannis

Keyword(s):

Body Weight ◽

Antifungal Activity ◽

Amphotericin B ◽

Murine Model ◽

Liposomal Amphotericin ◽

Invasive Pulmonary Aspergillosis ◽

Pulmonary Aspergillosis ◽

Amphotericin B Deoxycholate ◽

Immunomodulatory Properties ◽

Immunosuppressed Mice

ABSTRACT In a nonneutropenic murine model of invasive pulmonary aspergillosis, pretreatment with empty liposomes (E-lipo) was nearly as effective as 10 mg/kg of body weight liposomal amphotericin B and superior to 1 mg/kg amphotericin B deoxycholate. The beneficial immunomodulatory properties of E-lipo appear to compensate for their lack of direct antifungal activity.

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Sequential treatment of deep fungal infections with amphotericin B deoxycholate and amphotericin B colloidal dispersion

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/bf01708233 ◽

1997 ◽

Vol 16 (7) ◽

pp. 507-511 ◽

Cited By ~ 4

Author(s):

B. Beović ◽

T. Lejko-Zupanc ◽

J. Pretnar

Keyword(s):

Amphotericin B ◽

Fungal Infections ◽

Colloidal Dispersion ◽

Sequential Treatment ◽

Amphotericin B Deoxycholate

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Analisi Costo-Efficacia di Amfotericina B Liposomiale (L-AmB) versus Amfotericina B Complesso Lipidico (ABLC) nel trattamento empirico della neutropenia febbrile

Farmeconomia Health economics and therapeutic pathways ◽

10.7175/fe.v6i4.851 ◽

2005 ◽

Vol 6 (4) ◽

pp. 333-347

Author(s):

Mario Eandi

Keyword(s):

Febrile Neutropenia ◽

Amphotericin B ◽

Broad Spectrum ◽

Cost Minimization ◽

Colloidal Dispersion ◽

Lipid Complex ◽

Fungicidal Action ◽

Amphotericin B Deoxycholate ◽

Lipid Formulations ◽

Compromised Patients

Current international guidelines for the management of immuno-compromised patients with febrile neutropenia recommend a systemic antimicrobial therapy if fever hasn’t receded after three days of antibiotic treatment. Amphotericin B remains the gold standard because of its broad spectrum fungicidal action and minimal resistance development risk. Nonetheless, therapeutic use of the standard formulation, Amphotericin B deoxycholate, is limited by its toxicity, especially on the kidneys. To counteract this, amphotericin B has been encapsulated in liposomes, a process which reduces its toxicity and allows higher doses to be given. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (L-AmB). These lipid formulations differ in pharmacodynamics and pharmacokinetics, and can’t therefore be considered interchangeable. Besides, they are more expensive than Amphotericin B deoxycholate. Aim of the study is to perform a cost/effectiveness analysis (CEA) comparing L-AmB (3mg/kg/die or 5mg/kg/ die) and ABLC (5mg/kg/die) as first-line antimicrobial empirical treatments in immuno-compromised patients with febrile neutropenia resistant to broad spectrum antibiotics. Secondly, we present a cost-minimization analysis (CMA) of the considered alternatives, assuming the same efficacy for all treatments. At the end we value the principal cost items from the point of view of the Italian Health Service, with a particular focus on the economic burden caused by adverse reactions.

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