scholarly journals Distribution of Lipid Formulations of Amphotericin B into Bone Marrow and Fat Tissue in Rabbits

2000 ◽  
Vol 44 (2) ◽  
pp. 408-410 ◽  
Author(s):  
Andreas H. Groll ◽  
Diana Mickiene ◽  
Stephen C. Piscitelli ◽  
Thomas J. Walsh
Keyword(s):  
Bone Marrow ◽  
Amphotericin B ◽  
High Performance ◽  
Fungal Infections ◽  
Colloidal Dispersion ◽  
Fat Tissue ◽  
Marrow Fat ◽  
Lipid Complex ◽  
High Concentrations ◽  
Lipid Formulations

ABSTRACT The distribution of the three currently available lipid formulations of amphotericin B (AmB) into bone marrow and fat tissue was evaluated in noninfected rabbits. Groups of four animals each received either 1 mg of AmB deoxycholate (D-AmB) per kg of body weight per day or 5 mg of AmB colloidal dispersion, AmB lipid complex, or liposomal AmB per kg per day for seven doses. Plasma, bone marrow, fat, and liver were collected at autopsy, and AmB concentrations were determined by high-performance liquid chromatography. At the investigated dosages of 5 mg/kg/day, all AmB lipid formulations achieved at least fourfold-higher concentrations in bone marrow than did standard D-AmB at a dosage of 1 mg/kg/day. Concentrations in bone marrow were 62 to 76% of concurrent AmB concentrations in the liver. In contrast, all AmB formulations accumulated comparatively poorly in fat tissue. The results of this study show that high concentrations of AmB can be achieved in the bone marrow after administration of lipid formulations, suggesting their particular usefulness against disseminated fungal infections involving the bone marrow and against visceral leishmaniasis.

scholarly journals Effects of Lipid Formulations of Amphotericin B on Activity of Human Monocytes against Aspergillus fumigatus

2006 ◽  
Vol 50 (3) ◽  
pp. 868-873 ◽  
Author(s):  
J. Dotis ◽  
M. Simitsopoulou ◽  
M. Dalakiouridou ◽  
T. Konstantinou ◽  
A. Taparkou ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Colloidal Dispersion ◽  
Early Event ◽  
Human Monocytes ◽  
Xtt Assay ◽  
Lipid Complex ◽  
Production Of Hydrogen ◽  
Flow Cytometric Measurement ◽  
Lipid Formulations

ABSTRACT The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex, and amphotericin B colloidal dispersion (ABCD) on antifungal activity of human monocytes (MNCs), an important component of antifungal host defense, against Aspergillus fumigatus were compared to those of deoxycholate amphotericin B (DAMB). MNCs from healthy volunteers were incubated with 1 or 5 μg/ml DAMB and 5 or 25 μg/ml lipid formulations for 22 h. Drug-pretreated or untreated MNCs were then washed and assayed for the following: (i) activity against A. fumigatus hyphae by XTT assay at MNC:hypha ratios of 10:1 and 20:1; (ii) production of superoxide anion (O2 −) from MNCs in response to hyphae by cytochrome c reduction; (iii) production of hydrogen peroxide (H2O2) and H2O2-dependent intracellular intermediates (DIIs), such as OH− and HOCl, from MNCs in response to A. fumigatus culture supernatant by flow cytometric measurement of dihydrorhodamine-1,2,3 oxidation. With the exception of 1 μg/ml DAMB and 5 μg/ml LAMB or ABCD at 10:1, all amphotericin B formulations at both concentrations and MNC:hypha ratios enhanced MNC-induced damage of A. fumigatus hyphae compared to results with untreated cells (P < 0.01). While MNC O2 − production upon hyphal challenge, an early event in oxidative burst, was not affected by the drugs, production of H2O2 and DIIs, late events, were significantly increased by all four drugs (P < 0.01). At clinically relevant concentrations, both conventional amphotericin B and its lipid formulations enhance antihyphal activity of MNCs against A. fumigatus in association with significant augmentation of H2O2 and DIIs but not O2 −, further demonstrating the immunomodulatory antifungal activities of these agents.

scholarly journals Pulmonary Epithelial Lining Fluid Concentrations after Use of Systemic Amphotericin B Lipid Formulations

2009 ◽  
Vol 53 (11) ◽  
pp. 4934-4937 ◽  
Author(s):  
Stefan Weiler ◽  
Gerda Falkensammer ◽  
Angelika Hammerer-Lercher ◽  
Markus Anliker ◽  
Helene Vogelsinger ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Colloidal Dispersion ◽  
Standard Errors ◽  
Epithelial Lining ◽  
Lipid Complex ◽  
Epithelial Lining Fluid ◽  
Lipid Formulations

ABSTRACT Amphotericin B (AMB) concentrations were determined in pulmonary epithelial lining fluid (ELF) of 44 critically ill patients, who were receiving treatment with liposomal AMB (LAMB) (n = 11), AMB colloidal dispersion (ABCD) (n = 28), or AMB lipid complex (ABLC) (n = 5). Mean AMB levels (± standard errors of the means) in ELF amounted to 1.60 ± 0.58, 0.38 ± 0.07, and 1.29 ± 0.71 μg/ml in LAMB-, ABCD-, and ABLC-treated patients, respectively (differences are not significant).

scholarly journals Penetration of Amphotericin B Lipid Formulations into Pleural Effusion

2007 ◽  
Vol 51 (11) ◽  
pp. 4211-4213 ◽  
Author(s):  
Stefan Weiler ◽  
Rosa Bellmann-Weiler ◽  
Michael Joannidis ◽  
Romuald Bellmann
Keyword(s):  
Pleural Effusion ◽  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Colloidal Dispersion ◽  
Pleural Effusions ◽  
Lipid Complex ◽  
Penetration Ratio ◽  
Lipid Formulations

ABSTRACT The penetration of the amphotericin B (AMB) lipid formulations (liposomal AMB, AMB colloidal dispersion, and AMB lipid complex formulations) into pleural effusions in seven critically ill patients was assessed. AMB was detected in all pleural effusion samples at concentrations ranging from 0.02 to 0.43 μg/ml. The penetration ratio was 3 to 44%.

COMPARATIVE EFFECTIVENESS AND SAFETY BETWEEN AMPHOTERICIN B LIPID-FORMULATIONS: A SYSTEMATIC REVIEW

2018 ◽  
Vol 34 (3) ◽  
pp. 343-351 ◽  
Author(s):  
Luiza Raquel Grazziotin ◽  
Leila Beltrami Moreira ◽  
Maria Angelica Pires Ferreira
Keyword(s):  
Systematic Review ◽  
Renal Impairment ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Cochrane Library ◽  
Inclusion Criteria ◽  
Lipid Complex ◽  
Significant Difference ◽  
Safety Outcomes ◽  
Lipid Formulations

Objectives:It is not yet established the advantages between amphotericin B lipid complex (ABLC) and liposomal (L-AmB) in patients with invasive fungal infections refractory to usual doses of conventional AmB (d-AmB), previous renal impairment, or unacceptable d-AmB renal toxicity. This systematic review aims to compare ABLC and L-AmB effectiveness and safety outcomes in these subgroups of patients.Methods:The search was performed on Medline, Cochrane Library, EMBASE, and LILACS databases. Inclusion criteria: treatment comparing L-AmB with ABLC; patients who had (i) refractory infection after being treated with d-AmB, (ii) previous renal impairment, or (iii) unacceptable d-AmB toxicity. Two investigators independently screened the search results, assessed trial quality, and extracted data. A total of 1,054 articles were identified in the literature. Among those, eleven were selected for full-text reading and five met the inclusion criteria.Results:The five articles included reported on four separate observational studies. Overall, no significant difference was found in clinical relevant outcomes as new-onset dialysis, length of hospital stay, or mortality when comparing both lipid formulations. The studies reported a trend toward lower nephrotoxicity in patients treated with L-AmB. However, the results were imprecise and heterogeneous and the studies presented important methodological biases.Conclusions:The studies included in this systematic review pointed toward less nephrotoxicity events in the L-AmB group. However, due to low quality of evidence and no statistically significant differences in other clinical relevant outcomes, there is no definitive evidence of overall superiority in effectiveness or safety outcomes regarding one lipid formulation or another in this population subgroup.

scholarly journals Compartmentalized Intrapulmonary Pharmacokinetics of Amphotericin B and Its Lipid Formulations

2006 ◽  
Vol 50 (10) ◽  
pp. 3418-3423 ◽  
Author(s):  
Andreas H. Groll ◽  
Caron A. Lyman ◽  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Derek Armstrong ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Lung Tissue ◽  
Colloidal Dispersion ◽  
Pharmacokinetic Parameters ◽  
Dilution Method ◽  
Lipid Complex ◽  
Drug Concentrations ◽  
Amphotericin B Deoxycholate ◽  
Amphotericin B Lipid Complex ◽  
Lipid Formulations

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.

scholarly journals Comparative Efficacies, Toxicities, and Tissue Concentrations of Amphotericin B Lipid Formulations in a Murine Pulmonary Aspergillosis Model

2006 ◽  
Vol 50 (6) ◽  
pp. 2122-2131 ◽  
Author(s):  
Jon A. Olson ◽  
Jill P. Adler-Moore ◽  
Julie Schwartz ◽  
Gerard M. Jensen ◽  
Richard T. Proffitt
Keyword(s):  
Amphotericin B ◽  
High Performance ◽  
Therapeutic Index ◽  
Pulmonary Aspergillosis ◽  
Lipid Complex ◽  
Drug Concentrations ◽  
Kidney Morphology ◽  
Amphotericin B Lipid Complex ◽  
Effective Use ◽  
Lipid Formulations

ABSTRACT Invasive aspergillosis, an important cause of morbidity and mortality in immunosuppressed (IS) patients, is often treated with amphotericin B lipid formulations. In the present study, liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) were compared in treatment of murine pulmonary aspergillosis. Uninfected, IS mice were treated for 4 days with 1, 4, 8, or 12 mg L-AMB or ABLC/kg of body weight, and their lungs were analyzed by high-performance liquid chromatography for drug concentrations. IS mice intranasally challenged with Aspergillus fumigatus were treated with 12, 15, or 20 mg/kg L-AMB or ABLC and monitored for survival, fungal burden (CFU), and tissue drug concentration. Blood urea nitrogen (BUN) levels and kidney histopathology were determined for uninfected and infected mice given 15 or 20 mg/kg L-AMB or ABLC. The results showed that both drugs had therapeutic levels of drug (>3.0 μg/g) in the lungs of uninfected or infected mice, and 24 h after the last dose, ABLC levels were significantly higher than L-AMB levels (P < 0.02). L-AMB and ABLC at 12 mg/kg both produced 57% survival, but only L-AMB at 15 or 20 mg/kg further increased survival to 80 to 90%, with BUN levels and kidney morphology similar to those of controls. Survival at 15 or 20 mg/kg ABLC was not significantly different than that of controls, and BUN levels were significantly elevated, with tubular alterations in uninfected animals and acute necrosis in kidney tubules of infected animals. In conclusion, although both drugs were effective in prolonging survival at 12 mg/kg, the reduced nephrotoxicity of L-AMB increased its therapeutic index, allowing for its safe and effective use at 15 or 20 mg/kg.

scholarly journals Efficacies of Amphotericin B (AMB) Lipid Complex, AMB Colloidal Dispersion, Liposomal AMB, and Conventional AMB in Treatment of Murine Coccidioidomycosis

2004 ◽  
Vol 48 (6) ◽  
pp. 2140-2143 ◽  
Author(s):  
Gloria M. González ◽  
Rolando Tijerina ◽  
Laura K. Najvar ◽  
Rosie Bocanegra ◽  
Michael G. Rinaldi ◽  
...  
Keyword(s):  
Treatment Group ◽  
Amphotericin B ◽  
Murine Model ◽  
Therapeutic Efficacy ◽  
Colloidal Dispersion ◽  
Prolonged Survival ◽  
Lipid Complex ◽  
Fungal Load ◽  
Higher Doses ◽  
Lipid Formulations

ABSTRACT The therapeutic efficacy of three lipid formulations of amphotericin B was compared with that of conventional amphotericin B in treatment of murine coccidioidomycosis. All treatments prolonged survival compared with the no-treatment group (P < 0.0001). Although conventional amphotericin B was more active than lipid formulations on reducing quantitative fungal load on a milligram-per-kilogram basis (P < 0.003 to 0.0002), the lipid preparations could be administered at higher doses, sterilizing liver and spleen tissues. The efficacies of the lipid preparations were similar in this murine model of coccidioidomycosis.

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

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.

Two-year Longitudinal Evaluation of Amphotericin B Lipid Complex Injection in a Tertiary Care Medical Center

2000 ◽  
Vol 35 (2) ◽  
pp. 176-181 ◽  
Author(s):  
Leanne D. Kennedy ◽  
Julie F. Connelly ◽  
Kevin M. Kuzma
Keyword(s):  
Serum Creatinine ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Tertiary Care ◽  
Serum Creatinine Concentration ◽  
Creatinine Concentration ◽  
Lipid Complex ◽  
Tertiary Care Medical Center ◽  
Amphotericin B Lipid Complex ◽  
The Mean

A 2-year concurrent drug use evaluation was conducted in 156 patients to determine whether Abelcet (amphotericin B lipid complex injection) was being prescribed according to institution-approved guidelines and to characterize the patient population receiving Abelcet. Eighty-nine patients (57%) had fungal infections documented by chest x-ray, computed tomography, or fungal cultures. Sixty-seven (43%) had clinically suspected fungal infections. The Abelcet mean dose by weight was 5 mg/kg/day (actual body weight). Seventy-one patients (46%) met the established guidelines for use; 85 (54%) did not. Premedication was given to 64% of the patients; only 15 patients (10%) experienced documented fever and chills. A total of 72 patients (46%) died during therapy. Of the 75 patients who completed therapy in the hospital, 41 were switched to conventional amphotericin B, fluconazole, or itraconazole following a decrease in serum creatinine concentration, and 34 did not receive further antifungal therapy. The mean length of Abelcet therapy was 11 days. The mean increase in serum creatinine concentration at discontinuation of therapy was 0.2 mg/dL. Continued monitoring of Abelcet use was recommended and established guidelines were reaffirmed. Hydration with normal saline before and after dosing was suggested to help improve renal function, and dopamine was recommended to increase renal blood flow.

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