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%.

scholarly journals Pharmacokinetics of Amphotericin B Colloidal Dispersion in Critically Ill Patients with Cholestatic Liver Disease

2012 ◽  
Vol 56 (10) ◽  
pp. 5414-5418 ◽  
Author(s):  
Stefan Weiler ◽  
Elisabeth Überlacher ◽  
Julia Schöfmann ◽  
Eva Stienecke ◽  
Stefan Dunzendorfer ◽  
...  
Keyword(s):  
Steady State ◽  
Liver Disease ◽  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Normal Liver ◽  
Colloidal Dispersion ◽  
Cholestatic Liver Disease ◽  
Normal Liver Function ◽  
Standard Dosage

ABSTRACTThe pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD.

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 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.

Reliability of mini-bronchoalveolar lavage for the measurement of epithelial lining fluid concentrations of tobramycin in critically ill patients

2007 ◽  
Vol 33 (9) ◽  
pp. 1519-1523 ◽  
Author(s):  
Emmanuel Boselli ◽  
Dominique Breilh ◽  
Sarah Djabarouti ◽  
Christian Guillaume ◽  
Thomas Rimmelé ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid

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.

Pharmacokinetics of amphotericin B lipid complex in critically ill patients undergoing continuous venovenous haemodiafiltration

2013 ◽  
Vol 42 (4) ◽  
pp. 335-342 ◽  
Author(s):  
Maeve E. Malone ◽  
Owen I. Corrigan ◽  
Pierce V. Kavanagh ◽  
Caitriona Gowing ◽  
Maria Donnelly ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex

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.

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