scholarly journals Combination Therapy with Amphotericin B Lipid Complex and Caspofungin Acetate of Disseminated Zygomycosis in Diabetic Ketoacidotic Mice

2005 ◽  
Vol 49 (2) ◽  
pp. 830-832 ◽  
Author(s):  
Brad Spellberg ◽  
Yue Fu ◽  
John E. Edwards ◽  
Ashraf S. Ibrahim
Keyword(s):  
Combination Therapy ◽  
Amphotericin B ◽  
Rhizopus Oryzae ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex ◽  
Organ Clearance

ABSTRACT We studied the combination of amphotericin B lipid complex (ABLC) and caspofungin in mice with disseminated Rhizopus oryzae. Combination therapy improved survival compared to that of mice given monotherapy and that of untreated controls (P < 0.05) but did not improve organ clearance. In addition, prophylactic combination therapy was not more effective than prophylactic ABLC alone.

scholarly journals Comparative Pharmacodynamics of Amphotericin B Lipid Complex and Liposomal Amphotericin B in a Murine Model of Pulmonary Mucormycosis

2009 ◽  
Vol 54 (3) ◽  
pp. 1298-1304 ◽  
Author(s):  
Russell E. Lewis ◽  
Nathan D. Albert ◽  
Guangling Liao ◽  
Jingguo Hou ◽  
Randall A. Prince ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Rhizopus Oryzae ◽  
Tissue Concentration ◽  
Liposomal Amphotericin B ◽  
Tissue Concentrations ◽  
Lipid Complex ◽  
Pulmonary Mucormycosis ◽  
Amphotericin B Lipid Complex

ABSTRACT We compared the kinetics of amphotericin B (AMB) lung accumulation and fungal clearance by liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) in a neutropenic murine model of invasive pulmonary mucormycosis (IPM). Immunosuppressed BALB/c mice were inoculated with 1 × 106 Rhizopus oryzae spores and administered L-AMB or ABLC at daily intravenous doses of 1, 5, or 10 mg/kg of body weight for 5 days starting 12 h after infection. At a dose of 10 mg/kg/day, both L-AMB and ABLC were effective at reducing the R. oryzae lung fungal burden and achieved lung tissue concentrations exceeding the isolate mean fungicidal concentration (MFC) of 8 μg/ml by 72 h. When ABLC was dosed at 5 mg/kg/day, the ABLC-treated animals had significantly higher AMB lung concentrations than the L-AMB treated animals at 24 h (6.64 and 1.44 μg/g, respectively; P = 0.013) and 72 h (7.49 and 1.03 μg/g, respectively; P = 0.005), and these higher concentrations were associated with improved fungal clearance, as determined by quantitative real-time PCR (mean conidial equivalent of R. oryzae DNA per lung, 4.44 ± 0.44 and 6.57 ± 0.74 log10, respectively; P < 0.001). Analysis of the AMB tissue concentration-response relationships revealed that the suppression of R. oryzae growth in the lung required tissue concentrations that approached the MFC for the infecting isolate (50% effective concentration, 8.19 μg/g [95% confidence interval, 2.81 to 18.1 μg/g]). The rates of survival were similar in the animals treated with L-AMB and ABLC at 10 mg/kg/day. These data suggest that higher initial doses may be required during L-AMB treatment than during ABLC treatment of experimental IPM.

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.

Amphotericin B Lipid Complex

Drugs ◽  
2004 ◽  
Vol 64 (17) ◽  
pp. 1905-1911 ◽  
Author(s):  
David R Goldsmith ◽  
Caroline M Perry
Keyword(s):  
Amphotericin B ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex

scholarly journals Combination Echinocandin-Polyene Treatment of Murine Mucormycosis

2008 ◽  
Vol 52 (4) ◽  
pp. 1556-1558 ◽  
Author(s):  
Ashraf S. Ibrahim ◽  
Teclegiorgis Gebremariam ◽  
Yue Fu ◽  
John E. Edwards ◽  
Brad Spellberg
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Class Effect ◽  
Lipid Complex ◽  
Enhanced Activity ◽  
Amphotericin B Lipid Complex ◽  
Disseminated Mucormycosis

ABSTRACT We previously found that caspofungin synergized with amphotericin B lipid complex in treating murine mucormycosis. We now report a similarly enhanced activity of liposomal amphotericin combined with micafungin or anidulafungin in mice with disseminated mucormycosis. The efficacy of combination echinocandin-polyene therapy for mucormycosis is a class effect.

scholarly journals Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): combined experience from phase I and phase II studies.

1997 ◽  
Vol 41 (10) ◽  
pp. 2201-2208 ◽  
Author(s):  
A Adedoyin ◽  
J F Bernardo ◽  
C E Swenson ◽  
L E Bolsack ◽  
G Horwith ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Interindividual Variability ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Lipid Complex ◽  
Phase Ii Studies ◽  
Amphotericin B Lipid Complex ◽  
Trough Concentrations ◽  
Dose Limiting Toxicity ◽  
Wide Interindividual Variability

Amphotericin B (AmB) has been the most effective systemic antifungal agent, but its use is limited by the dose-limiting toxicity of the conventional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and include ABELCET (formerly ABLC), but their dispositions have not been well characterized; hence, the reason for their improved profiles remains unclear. This report details the pharmacokinetics of ABELCET examined in various pharmacokinetic and efficacy studies by using whole-blood measurements of AmB concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of AmB after administration of ABELCET is different from that after administration of Fungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interindividual variability, extensive distribution, and low clearance. The pharmacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple dosings increased less than proportionately with dose, steady state appeared to have been attained in 2 to 3 days, despite an estimated half-life of up to 5 days, and there was no evidence of significant accumulation in the blood. The data are internally consistent, even though they were gathered under different conditions and circumstances. The pharmacokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for its improved toxicity profile compared to those of conventional formulations.

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