scholarly journals In Vitro and In Vivo Antifungal Activity of Amphotericin B Lipid Complex: Are Phospholipases Important?

1998 ◽  
Vol 42 (4) ◽  
pp. 767-771 ◽  
Author(s):  
Christine E. Swenson ◽  
Walter R. Perkins ◽  
Patricia Roberts ◽  
Imran Ahmad ◽  
Rachel Stevens ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Vascular Tissue ◽  
Therapeutic Index ◽  
Test Material ◽  
Lipid Complex ◽  
In Vitro Susceptibility ◽  
Amphotericin B Lipid Complex

ABSTRACT Amphotericin B lipid complex for injection (ABLC) is a suspension of amphotericin B complexed with the lipidsl-α-dimyristoylphosphatidylcholine (DMPC) andl-α-dimyristoylphosphatidylglycerol. ABLC is less toxic than amphotericin B deoxycholate (AmB-d), while it maintains the antifungal activity of AmB-d. Active amphotericin B can be released from ABLC by exogenously added (snake venom, bacteria, orCandida-derived) phospholipases or by phospholipases derived from activated mammalian vascular tissue (rat arteries). Such extracellular phospholipases are capable of hydrolyzing the major lipid in ABLC. Mutants of C. albicans that were resistant to ABLC but not AmB-d in vitro were deficient in extracellular phospholipase activity, as measured on egg yolk agar or as measured by their ability to hydrolyze DMPC in ABLC. ABLC was nevertheless effective in the treatment of experimental murine infections produced by these mutants. Isolates of Aspergillus species, apparently resistant to ABLC in vitro (but susceptible to AmB-d), were also susceptible to ABLC in vivo. We suggest that routine in vitro susceptibility tests with ABLC itself as the test material may not accurately predict the in vivo activity of ABLC and that the enhanced therapeutic index of ABLC relative to that of AmB-d in vivo may be due, in part, to the selective release of active amphotericin B from the complex at sites of fungal infection through the action of fungal or host cell-derived phospholipases.

scholarly journals Behavior of amphotericin B lipid complex in plasma in vitro and in the circulation of rats.

1997 ◽  
Vol 41 (5) ◽  
pp. 886-892 ◽  
Author(s):  
R Bhamra ◽  
A Sa'ad ◽  
L E Bolcsak ◽  
A S Janoff ◽  
C E Swenson
Keyword(s):  
Amphotericin B ◽  
Therapeutic Index ◽  
Parent Material ◽  
Protein Distribution ◽  
Time Curve ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex ◽  
Reduced Toxicity

Amphotericin B lipid complex (ABLC) shows reduced toxicity relative to that of amphotericin B deoxycholate (AmB-d) while maintaining antifungal activity. Rat blood or plasma was spiked with ABLC in vitro. Released amphotericin B was separated from the parent material by centrifugation. At early times (0 to 15 min) most (approximately 90%) of the amphotericin B was complexed. The amount of released amphotericin B increased gradually in a time- and temperature-dependent fashion. The released amphotericin B was associated with plasma lipoprotein and nonlipoprotein proteins. The area under the concentration-time curve from 0 to 24 h for total amphotericin B in whole blood of rats given a single intravenous bolus dose of 1 mg of ABLC per kg of body weight was fourfold lower than that in rats given 1 mg of AmB-d per kg. The complexed amphotericin B was rapidly removed from the circulation and was distributed to the tissues in these rats. Other rats were treated intravenously with ABLC (10 mg/kg/day) or AmB-d (0.5 mg/kg/day) daily for 15 days. Blood was collected at 15 and 180 min after administration of the last dose. The total levels of amphotericin B in the blood of the group given ABLC were about three to five times those in the group given AmB-d, and the concentration of released, protein-bound amphotericin B in the plasma of the group given ABLC was about one to two times that observed for the group given AmB-d, despite the 20-fold difference in dose. The relative protein distribution of amphotericin B in plasma was similar after ABLC or AmB-d administration under these steady-state conditions in vivo. The rapid uptake of complexed amphotericin B by tissues and the very low levels of circulating protein-bound amphotericin B in plasma after the administration of ABLC may explain, in part, the reduced toxicity and enhanced therapeutic index of this preparation.

scholarly journals Fungal Phospholipase Activity and Susceptibility to Lipid Preparations of Amphotericin B

2001 ◽  
Vol 45 (11) ◽  
pp. 3231-3233 ◽  
Author(s):  
Magnus Gottfredsson ◽  
Chad J. Jessup ◽  
Gary M. Cox ◽  
John R. Perfect ◽  
Mahmoud A. Ghannoum
Keyword(s):  
Candida Albicans ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Susceptibility Testing ◽  
Phospholipase Activity ◽  
Lipid Complex ◽  
In Vitro Susceptibility ◽  
Amphotericin B Lipid Complex ◽  
In Vitro Susceptibility Testing

ABSTRACT It has been postulated that phospholipases of fungal origin can affect in vitro susceptibility testing of amphotericin B lipid complex (ABLC). We used specific phospholipase-deficient mutants ofCandida albicans and Cryptococcus neoformans in susceptibility testing and demonstrated that extracellular fungal phospholipase activity does not influence the in vitro susceptibilities of these two fungi to ABLC.

Comparative in vitro Antifungal Activity of Amphotericin B Lipid Complex, Amphotericin B and Fluconazole

Chemotherapy ◽  
2000 ◽  
Vol 46 (4) ◽  
pp. 235-244 ◽  
Author(s):  
Alfonso-Javier Carrillo-Muñoz ◽  
Guillermo Quindós ◽  
Cristina Tur ◽  
Maite Ruesga ◽  
Rocío Alonso ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex ◽  
In Vitro Antifungal Activity

In vitro and in vivo antifungal activities of liposomal amphotericin B, and amphotericin B lipid complex

1994 ◽  
Vol 128 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Kotaro Mitsutake ◽  
Shigeru Kohno ◽  
Yoshitsugu Miyazaki ◽  
Tetsuhiro Noda ◽  
Haruko Miyazaki ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
Lipid Complex ◽  
Antifungal Activities ◽  
Amphotericin B Lipid Complex

scholarly journals In Vitro and In Vivo Antifungal Activity of AmBisome Compared to Conventional Amphotericin B and Fluconazole against Candida auris

2021 ◽  
Author(s):  
Janet Herrada ◽  
Ahmed Gamal ◽  
Lisa Long ◽  
Sonia P. Sanchez ◽  
Thomas S. McCormick ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Kidney Tissue ◽  
Treated Group ◽  
Untreated Group ◽  
Candida Auris ◽  
Fungal Burden ◽  
In Vivo Antifungal Activity

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo. AmBisome showed MIC50 and MIC90 values of 1 and 2 μg/mL, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg -treated group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data shows that AmBisome shows significant antifungal activity against C. auris in vitro as well as in vivo.

scholarly journals Dose Range Evaluation of Liposomal Nystatin and Comparisons with Amphotericin B and Amphotericin B Lipid Complex in Temporarily Neutropenic Mice Infected with an Isolate of Aspergillus fumigatus with Reduced Susceptibility to Amphotericin B

1999 ◽  
Vol 43 (11) ◽  
pp. 2592-2599 ◽  
Author(s):  
David W. Denning ◽  
Peter Warn
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Dose Range ◽  
Respiratory Arrest ◽  
Optimal Dosage ◽  
Lipid Complex ◽  
Amphotericin B Deoxycholate ◽  
Liver And Kidney ◽  
Amphotericin B Lipid Complex

ABSTRACT Using an isolate of Aspergillus fumigatus that is less susceptible in vivo to amphotericin B than most other isolates, we compared different doses of liposomal nystatin (L-nystatin), liposomal amphotericin B (L-amphotericin), and amphotericin B lipid complex (ABLC) with amphotericin B deoxycholate. Four experiments with intravenously infected neutropenic mice were conducted. A dose of L-nystatin at 10 mg/kg of body weight was toxic (the mice had fits or respiratory arrest). The optimal dosage of L-nystatin was 5 mg/kg daily on days 1, 2, 4, and 7 (90% survival). This was superior to L-amphotericin (5 mg/kg [P = 0.24] and 1 mg/kg [P < 0.0001]), ABLC (5 mg/kg [P = 0.014] and 1 mg/kg [P < 0.0001]), and amphotericin B deoxycholate (5 mg/kg [P = 0.008]). In terms of liver and kidney cultures, L-nystatin (5 mg/kg) was superior to all other regimens (P = 0.0032 and <0.0001, respectively). Higher doses of L-amphotericin (25 and 50 mg/kg) in one earlier experiment were more effective (100% survival) than 1 mg of L-amphotericin per kg and amphotericin deoxycholate (5 mg/kg) in terms of mortality and both liver and kidney culture results and to L-amphotericin (5 mg/kg) in terms of liver and kidney culture results only. ABLC (25 mg/kg) given daily for 7 days was superior to ABLC (50 mg/kg [P = 0.03]) but not to ABLC at 5 mg/kg or amphotericin B deoxycholate in terms of mortality, although it was in terms of liver and kidney culture results. No dose-response for amphotericin B (5 and 1 mg/kg) was demonstrable. In conclusion, in this stringent model, high doses of L-amphotericin and ABLC could overcome reduced susceptibility to amphotericin B deoxycholate, but all were inferior to 5- to 10-fold lower doses of L-nystatin.

In-Vitro and In-Vivo Studies on Novel Chitosan-g-Pluronic F-127 Copolymer Based Nanocarrier of Amphotericin B for Improved Antifungal Activity

2014 ◽  
Vol 4 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Vivek Kumar ◽  
Pramod K. Gupta ◽  
Vivek K. Pawar ◽  
Ashwni Verma ◽  
Renuka Khatik ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B

scholarly journals Pharmacokinetics and Pharmacodynamics of Amphotericin B Deoxycholate, Liposomal Amphotericin B, and Amphotericin B Lipid Complex in an In Vitro Model of Invasive Pulmonary Aspergillosis

2010 ◽  
Vol 54 (8) ◽  
pp. 3432-3441 ◽  
Author(s):  
Jodi M. Lestner ◽  
Susan J. Howard ◽  
Joanne Goodwin ◽  
Lea Gregson ◽  
Jayesh Majithiya ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Host Cells ◽  
Pulmonary Aspergillosis ◽  
Lipid Complex ◽  
Amphotericin B Deoxycholate ◽  
Amphotericin B Lipid Complex

ABSTRACT The pharmacodynamic and pharmacokinetic (PK-PD) properties of amphotericin B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an in vitro model of IPA to further elucidate the PK-PD of amphotericin B deoxycholate (DAmB), liposomal amphotericin B (LAmB) and amphotericin B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated. Pharmacodynamic relationships were defined by measuring concentrations of galactomannan in endovascular and alveolar compartments. Confocal microscopy was used to visualize fungal biomass. A mathematical model was used to calculate the area under the concentration-time curve (AUC) in each compartment and estimate the extent of drug penetration. The interaction of LAmB with host cells and hyphae was visualized using sulforhodamine B-labeled liposomes. The MICs for the pure compound and the three formulations were comparable (0.125 to 0.25 mg/liter). For all formulations, concentrations of AmB progressively declined in the endovascular fluid as the drug distributed into the cellular bilayer. Depending on the formulation, the AUCs for AmB were 10 to 300 times higher within the cells than within endovascular fluid. The concentrations producing a 50% maximal effect (EC50) in the endovascular compartment were 0.12, 1.03, and 4.41 mg/liter for DAmB, LAmB, and ABLC, respectively, whereas, the EC50 in the alveolar compartment were 0.17, 7.76, and 39.34 mg/liter, respectively. Confocal microscopy suggested that liposomes interacted directly with hyphae and host cells. The PK-PD relationships of the three most widely used formulations of AmB differ markedly within an in vitro lung model of IPA.

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