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European Journal of Cancer & Clinical... Feb 1988
Review
Topics: Amphotericin B; Animals; Antineoplastic Agents; Drug Resistance; Drug Synergism; Humans; Mice
PubMed: 3281841
DOI: 10.1016/0277-5379(88)90241-6 -
International Journal of Pharmaceutics Sep 2010Amphotericin B was formulated in lipids (Nanosomal Amphotericin B) without using any detergent or toxic organic solvents during the preparation. Electron microscopy and...
Amphotericin B was formulated in lipids (Nanosomal Amphotericin B) without using any detergent or toxic organic solvents during the preparation. Electron microscopy and particle size determination of Nanosomal Amphotericin B showed a homogeneous population of nanosized particles below 100 nm. Hemolysis assay indicated that Nanosomal Amphotericin B causes significantly less lysis of red blood cells than Amphotericin B deoxycholate and was comparable to Ambisome. A maximum daily dose of Nanosomal Amphotericin B at 5 mg/kg in rabbits and 10 mg/kg in mice for 28 days showed no symptoms of toxicity, mortality or significant body weight reduction. Hematological and gross pathological analysis of tissues revealed no abnormalities attributable to the drug treatment. Nanosomal Amphotericin B and Ambisome were injected (iv) at 2 mg/kg consecutively for 5 days into mice infected with Aspergillus fumigatus. The treatment resulted in 90% survival with Nanosomal Amphotericin B and only 30% survival with Ambisome after 10 days of fungal infection. However, all of the 10 control mice which were not treated with Amphotericin B died within 5 days of fungal infection. Nanosomal Amphotericin B is safe, cost effective and provides an alternative option for treatment of fungal disease.
Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Female; Liposomes; Male; Mice; Mice, Mutant Strains; Nanoparticles; Rabbits
PubMed: 20621173
DOI: 10.1016/j.ijpharm.2010.07.003 -
Science Advances Jan 2021Ergosterol-targeting amphotericin B (AmB) is the first line of defense for life-threatening fungal infections. Two models have been proposed to illustrate AmB assembly...
Ergosterol-targeting amphotericin B (AmB) is the first line of defense for life-threatening fungal infections. Two models have been proposed to illustrate AmB assembly in the cell membrane; one is the classical ion channel model in which AmB vertically forms transmembrane tunnel and the other is a recently proposed sterol sponge model where AmB is laterally adsorbed onto the membrane surface. To address this controversy, we use polarization-sensitive stimulated Raman scattering from fingerprint C═C stretching vibration to visualize AmB, ergosterol, and lipid in single fungal cells. Intracellular lipid droplet accumulation in response to AmB treatment is found. AmB is located in membrane and intracellular droplets. In the 16 strains studied, AmB residing inside cell membrane was highly ordered, and its orientation is primarily parallel to phospholipid acyl chains, supporting the ion channel model. Label-free imaging of AmB and chemical contents offers an analytical platform for developing low-toxicity, resistance-refractory antifungal agents.
Topics: Amphotericin B; Candida; Ergosterol; Ion Channels; Spectrum Analysis, Raman
PubMed: 33523971
DOI: 10.1126/sciadv.abd5230 -
Antimicrobial Agents and Chemotherapy Nov 1989Amphotericin B is the most effective agent for the majority of systemic fungal infections but often causes toxicity, and specific dosage guidelines for amphotericin B in...
Amphotericin B is the most effective agent for the majority of systemic fungal infections but often causes toxicity, and specific dosage guidelines for amphotericin B in pediatric patients are lacking. The purpose of this study was to characterize the pharmacokinetics of amphotericin B in children. Twelve patients (mean age, 6.6 years; range, 4 months to 14 years) receiving amphotericin B, 0.68 +/- 0.34 mg/kg per day (mean plus or minus standard deviation), were studied. Four to eight blood samples were collected during a 24-h period and analyzed by high-pressure liquid chromatography. The peak concentration of amphotericin B in serum was 2.9 +/- 2.8 micrograms/ml. The mean total clearance, apparent volume of distribution, and elimination half-life were 0.46 +/- 0.20 ml/min per kg, 0.76 +/- 0.52 liters/kg, and 18.1 +/- 6.6 h, respectively. Total clearance decreased with age (p less than 0.01). In children aged 8 months to 9 years, the mean total clearance was 0.57 +/- 0.15 ml/min per kg, and in children older than 9 years, it was 0.24 +/- 0.02 ml/min per kg. Interpatient variation in the clearance and volume of distribution of amphotericin B was greater than threefold and greater than eightfold, respectively. However, pharmacokinetic parameters did not change in two stable patients who were studied again. Because clearance decreased substantially with age, older children may require lower doses of amphotericin B per kilogram to decrease the potential for toxicity.
Topics: Adolescent; Amphotericin B; Child; Child, Preschool; Chromatography, High Pressure Liquid; Creatinine; Female; Half-Life; Humans; Infant; Infusions, Intravenous; Male; Phlebitis
PubMed: 2610508
DOI: 10.1128/AAC.33.11.1989 -
The Journal of Antibiotics Apr 2019To find novel amphotericin B (AmB) derivatives with high therapeutic potential, low toxicity, and water solubility, a series of nine N-substituted AmB derivatives were...
To find novel amphotericin B (AmB) derivatives with high therapeutic potential, low toxicity, and water solubility, a series of nine N-substituted AmB derivatives were evaluated for their antifungal activity using the broth dilution method and for their hemolytic toxicity with sterile defibrinated sheep blood. Qualitative screening of the effect of the derivatives on two reference Candida albicans strains and of their solubility was performed based on the value of n (n is a positive integer), resulting in the identification of an optimal compound, NH-(AEEA)-AmB (DMR005; AEEA is 8-amino-3,6- dioxaoctanoic acid). Preliminary safety assessments of DMR005 were carried out via the MTT cell viability assay in vitro and acute toxicity assay in vivo. In general, DMR005 not only has higher water solubility and less toxicity than the parent polyene but also retains antifungal potency.
Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Cell Survival; Cytological Techniques; Disease Models, Animal; Erythrocytes; HEK293 Cells; Hemolysis; Humans; Microbial Sensitivity Tests; Poisoning; Sheep; Solubility
PubMed: 30635615
DOI: 10.1038/s41429-018-0138-8 -
Antibiotiki I Khimioterapiia =... 1997
Review
Topics: Amphotericin B; Antifungal Agents; Glycosylation; Microbial Sensitivity Tests; Molecular Conformation; Molecular Structure
PubMed: 9182506
DOI: No ID Found -
The Journal of Antimicrobial... Sep 1992The comparative activities of two preparations of amphotericin B against Coccidioides immitis were investigated. These preparations were a deoxycholate suspension... (Comparative Study)
Comparative Study
The comparative activities of two preparations of amphotericin B against Coccidioides immitis were investigated. These preparations were a deoxycholate suspension (conventional amphotericin B) and a lipid-based formulation, amphotericin B lipid complex (ABLC). In-vitro susceptibility testing demonstrated that the MICs of ABLC were < or = 0.25 mg/L and of conventional amphotericin B were 0.5 mg/L for C. immitis. However, conventional amphotericin B was at least four-fold more fungicidal, with a minimum fungicidal concentration of 4.0 vs > 16 mg/L for ABLC. The therapeutic efficacies were tested in murine models of acute systemic coccidioidomycosis. Female CD-1 mice were infected iv with C. immitis arthroconidia to establish high (> 50%) or low (< 50%) mortality models. Therapy with conventional amphotericin B or ABLC was given three times per week for two weeks starting three days post-infection. Controls received no therapy or drug-free diluent only. Survival was tallied up to 49 days post-infection and the fungal cfu counts in spleen, liver, and lungs of all survivors were determined. In the low mortality study all treated mice survived and all therapy regimens reduced infection in all organs. All mice given ABLC 6.6 or 13.2 mg/kg/dose and 80% given ABLC 16.5 mg/kg/dose, as well as 90% given conventional amphotericin B 0.66 mg/kg/dose were free of infection; all controls remained infected. In two high mortality studies, all mice given ABLC 0.66-20 mg/kg/dose or conventional amphotericin B 0.22 or 0.66 mg/kg/dose survived compared with 0-20% of controls. Thirty per cent of uninfected mice given ABLC 20 mg/kg/dose and 40% given conventional amphotericin B 2.0 mg/kg/dose died due to drug toxicity. Mice given ABLC or conventional amphotericin B had lower residual cfu counts of C. immitis in all organs than did controls. Sixty to one hundred per cent of mice given ABLC regimens > or = 6.6 mg/kg/dose were cured, whereas all controls and 50-60% of mice receiving the highest non-toxic conventional amphotericin B regimen (0.66 mg/kg/dose) remained infected. At equal non-toxic amphotericin B doses, conventional amphotericin B was more effective than ABLC in reducing cfu in infected organs.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Amphotericin B; Animals; Antifungal Agents; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Female; Mice; Microbial Sensitivity Tests
PubMed: 1452501
DOI: 10.1093/jac/30.3.353 -
Bone Marrow Transplantation 1994To lower amphotericin B-associated toxicity, amphotericin B may be integrated into liposomes (AmBisome) or can be administered in Intralipid 20% emulsions... (Clinical Trial)
Clinical Trial Comparative Study
To lower amphotericin B-associated toxicity, amphotericin B may be integrated into liposomes (AmBisome) or can be administered in Intralipid 20% emulsions (Ampho-B/Lipid). The present study compares the pharmacokinetic characteristics of standard amphotericin B dissolved in glucose 5% (Ampho-B/G) (n = 6) to the alternative formulations Ampho-B/Lipid (n = 8) and Ambisome (n = 10). Ampho-B/G and Ampho-B/Lipid were infused at a dose of 1 mg/kg, while the dose of AmBisome was increased to 3 mg/kg. Infusion duration was 1 h. Pharmacokinetics of Ampho-B/G, AmB/Lipid and AmBisome showed striking differences, specifically with regard to the respective Cmax and AUC values. In fact, after application of AmB/Lipid mean Cmax values were reduced to 39% and mean AUC values were lowered to 57% compared with application of Ampho-B/G in the same patients. This compares with a 1.8-fold greater Vss for Ampho-B/Lipid and a clearance rate which was 2.1-fold faster. By contrast, application of AmBisome (at a three-fold greater dose) resulted in Cmax and AUC values eight-fold and 12-fold greater than those reached by Ampho-B/G. The higher Cmax values achieved by AmBisome relate to a four-fold smaller Vss compared with Ampho-B/G. Assuming a linear relationship between AmBisome dose and Cmax, it was concluded that even at equal doses the liposomal formulation of amphotericin B would result in significantly greater Cmax and AUC values than Ampho-B/G or Ampho-B/Lipid.
Topics: Amphotericin B; Humans
PubMed: 7703929
DOI: No ID Found -
American Journal of Health-system... Jul 1995
Comparative Study
Topics: Amphotericin B; Chemical Precipitation; Drug Incompatibility; Fat Emulsions, Intravenous; Humans; Particle Size
PubMed: 7671046
DOI: 10.1093/ajhp/52.13.1463 -
The Custom R Group Enumeration with Various R Group Libraries at Designated Sites on Amphotericin B.Current Computer-aided Drug Design 2023Amphotericin B is a gold-standard drug, particularly for the treatment of systemic fungal infections. However, its low solubility and permeability limit its application....
BACKGROUND
Amphotericin B is a gold-standard drug, particularly for the treatment of systemic fungal infections. However, its low solubility and permeability limit its application. To improve its bioavailability, AmB may be conjugated with various water-soluble auxiliary groups.
METHODS
Custom R group Enumeration was used at the designated sites of Amphotericin B. The designated sites taken into consideration are the carboxyl moiety of the aglycone part and the amine moiety of the glycone part of Amphotericin B for Enumeration purposes. The enumerated molecules were subjected to QikProp properties.
RESULTS
We identified fourteen hits with improved predicted aqueous solubility and cell permeability.
CONCLUSION
Enumeration might be applicable in improving bioavailability, which could lead to the oral formulation of the Amphotericin B drug.
Topics: Humans; Amphotericin B; Antifungal Agents; Mycoses; Solubility
PubMed: 36694325
DOI: 10.2174/1573409919666230123144712