scholarly journals Long-Circulating Immunoliposomal Amphotericin B against Invasive Pulmonary Aspergillosis in Mice

1998 ◽  
Vol 42 (1) ◽  
pp. 40-44 ◽  
Author(s):  
Takakazu Otsubo ◽  
Kazuo Maruyama ◽  
Shigefumi Maesaki ◽  
Yoshitsugu Miyazaki ◽  
Eitaro Tanaka ◽  
...  
Keyword(s):  
Body Weight ◽  
Polyethylene Glycol ◽  
Amphotericin B ◽  
Marked Reduction ◽  
Survival Rates ◽  
Invasive Pulmonary Aspergillosis ◽  
Intravenous Dose ◽  
Pharmacokinetic Studies ◽  
Pulmonary Aspergillosis ◽  
Liposome Surface

ABSTRACT We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number ofAspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 μg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 μg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.

scholarly journals Efficacy of Single-Dose Liposomal Amphotericin B or Micafungin Prophylaxis in a Neutropenic Murine Model of Invasive Pulmonary Aspergillosis

2008 ◽  
Vol 52 (11) ◽  
pp. 4178-4180 ◽  
Author(s):  
Russell E. Lewis ◽  
Nathaniel D. Albert ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Liposomal Amphotericin B ◽  
Potential Utility ◽  
Pulmonary Aspergillosis ◽  
Fungal Burden ◽  
Animal Survival

ABSTRACT In a neutropenic murine model of invasive pulmonary aspergillosis, prophylaxis with single doses of liposomal amphotericin B or micafungin at ≥5 mg/kg of body weight improved animal survival and suppressed the lung fungal burden for up to 7 days after infection, demonstrating the potential utility of infrequent dosing with these antifungals.

scholarly journals Antifungal Activity of the Pradimicin Derivative BMS 181184 in the Treatment of Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits

1998 ◽  
Vol 42 (9) ◽  
pp. 2399-2404 ◽  
Author(s):  
Corina E. Gonzalez ◽  
Andreas H. Groll ◽  
Neelam Giri ◽  
Daiva Shetty ◽  
Ibrahim Al-Mohsen ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Drug Disposition ◽  
Tissue Injury ◽  
Invasive Pulmonary Aspergillosis ◽  
Dosage Level ◽  
Lavage Fluid ◽  
Pharmacokinetic Studies ◽  
Pulmonary Aspergillosis ◽  
Lung Weight ◽  
Dosing Regimens

ABSTRACT The activity of the pradimicin derivative BMS 181184 was evaluated in a model of invasive pulmonary aspergillosis in persistently neutropenic rabbits and compared with that of amphotericin B deoxycholate. BMS 181184 at total daily doses of 50 and 150 mg/kg of body weight was at least as effective as amphotericin B at 1 mg/kg once a day in conferring survival and had comparable activity in reducing organism-mediated tissue injury and excess lung weight. Although treatment at all dosing regimens of BMS 181184 resulted in significant reductions in fungal tissue burden compared to untreated controls, equivalence to amphotericin B occurred only at the higher dosage level. Similar observations were made in bronchoalveolar lavage fluid cultures obtained postmortem. Monitoring of the animals through ultrafast computerized tomography scan revealed a marked resolution of pulmonary lesions during treatment with BMS 181184. The compound was well tolerated at all dosing regimens, and no toxicity was noted. Pharmacokinetic studies revealed nonlinear drug disposition with increased clearance at higher dosages and some evidence for extravascular drug accumulation. BMS 181184 had excellent activity in the treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits, thus underscoring the potential of pradimicin derivatives in therapy of invasive aspergillosis in the neutropenic host.

scholarly journals Pretreatment with Empty Liposomes Attenuates the Immunopathology of Invasive Pulmonary Aspergillosis in Corticosteroid-Immunosuppressed Mice

2006 ◽  
Vol 51 (3) ◽  
pp. 1078-1081 ◽  
Author(s):  
Russell E. Lewis ◽  
Georgios Chamilos ◽  
Randall A. Prince ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Body Weight ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Amphotericin B Deoxycholate ◽  
Immunomodulatory Properties ◽  
Immunosuppressed Mice

ABSTRACT In a nonneutropenic murine model of invasive pulmonary aspergillosis, pretreatment with empty liposomes (E-lipo) was nearly as effective as 10 mg/kg of body weight liposomal amphotericin B and superior to 1 mg/kg amphotericin B deoxycholate. The beneficial immunomodulatory properties of E-lipo appear to compensate for their lack of direct antifungal activity.

scholarly journals In Vitro and In Vivo Activities of NS-718, a New Lipid Nanosphere Incorporating Amphotericin B, againstAspergillus fumigatus

1999 ◽  
Vol 43 (3) ◽  
pp. 471-475 ◽  
Author(s):  
Takakazu Otsubo ◽  
Shigefumi Maesaki ◽  
Mohammad Ashraf Hossain ◽  
Yoshihiro Yamamoto ◽  
Kazunori Tomono ◽  
...  
Keyword(s):  
Survival Rate ◽  
Amphotericin B ◽  
Low Dose ◽  
Invasive Pulmonary Aspergillosis ◽  
Pharmacokinetic Studies ◽  
In Vitro Activity ◽  
Pulmonary Aspergillosis ◽  
In Vivo Efficacy

ABSTRACT We evaluated the in vitro and in vivo potencies of a new lipid nanosphere that incorporates amphotericin B (AmB), NS-718, againstAspergillus fumigatus. The in vitro activity of NS-718 (the MIC at which 90% of strains are inhibited [MIC90], 0.25 μg/ml) against 18 isolates of A. fumigatus was similar to that of deoxycholate AmB (D-AmB; Fungizone; MIC90, 0.25 μg/ml), but NS-718 was more potent than liposomal AmB (L-AmB; AmBisome; MIC90, 1.0 μg/ml). The in vivo efficacy of NS-718 in a rat model of invasive pulmonary aspergillosis was compared with those of D-AmB and L-AmB. A low dose (1 mg/kg of body weight) of L-AmB was ineffective (survival rate, 0%), although equivalent doses of D-AmB and NS-718 were more effective (survival rate, 17%). However, a higher dose of NS-718 (3 mg/kg) was more effective (survival rate, 100%) than equivalent doses of D-AmB and L-AmB (survival rate, 0%). To explain these differences, pharmacokinetic studies showed higher concentrations of AmB in the plasma of rats treated with NS-718 than in the plasma of those treated with D-AmB. Our results suggest that NS-718, a new preparation of AmB, is a promising antifungal agent with activity against pulmonary aspergillosis.

scholarly journals Efficacy of Nebulized Liposomal Amphotericin B in Treatment of Experimental Pulmonary Aspergillosis

2005 ◽  
Vol 49 (7) ◽  
pp. 3028-3030 ◽  
Author(s):  
Joan Gavaldà ◽  
María-Teresa Martín ◽  
Pedro López ◽  
Xavier Gomis ◽  
José-Luís Ramírez ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Liposomal Amphotericin B ◽  
Pulmonary Aspergillosis ◽  
Lower Lung

ABSTRACT The efficacy of therapeutic aerosolized amphotericin B (AMB) was studied in a steroid-immunosuppressed murine model of invasive pulmonary aspergillosis. Nebulized liposomal AMB can be a valid approach to the treatment of this infection, with subjects showing significantly improved survival relative to that of subjects given intravenous deoxycholate AMB, as well as lower lung weights and pulmonary glucosamine levels.

scholarly journals Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis.

1997 ◽  
Vol 41 (3) ◽  
pp. 696-698 ◽  
Author(s):  
M Murphy ◽  
E M Bernard ◽  
T Ishimaru ◽  
D Armstrong
Keyword(s):  
Body Weight ◽  
Experimental Model ◽  
Antifungal Agent ◽  
Invasive Pulmonary Aspergillosis ◽  
Clinical Isolates ◽  
Aspergillus Species ◽  
Pulmonary Aspergillosis

Voriconazole, a new azole antifungal agent, showed potent activity against clinical isolates of Aspergillus spp. in vitro. For A. fumigatus, the MIC range was < 0.03 to 0.5 microgram/ml and the MIC at which 90% of isolates are inhibited was 0.25 microgram/ml. In an experimental model of invasive pulmonary aspergillosis which mimics infection in humans, oral voriconazole at dosages of 30 mg/kg of body weight per day significantly delayed or prevented mortality.

Fungal Lung Infections Treated by 5 Flucytosine

1982 ◽  
Vol 27 (3) ◽  
pp. 244-246
Author(s):  
R. P. Symonds ◽  
A. G. Robertson ◽  
L. M. Stewart ◽  
G. Boyd
Keyword(s):  
Amphotericin B ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Lung Infections

5 Flucytosine was used successfully to treat two patients with pulmonary candidiasis and, in combination with Amphotericin B, one patient with invasive pulmonary aspergillosis.

scholarly journals Accelerated Metabolism of Voriconazole and Its Partial Reversal by Cimetidine

2009 ◽  
Vol 53 (4) ◽  
pp. 1712-1714 ◽  
Author(s):  
Brad Moriyama ◽  
Jason Elinoff ◽  
Robert L. Danner ◽  
Juan Gea-Banacloche ◽  
Gennethel Pennick ◽  
...  
Keyword(s):  
Body Weight ◽  
Cytochrome P450 ◽  
Enzyme Inhibitor ◽  
Invasive Pulmonary Aspergillosis ◽  
Cytochrome P450 Enzyme ◽  
Pulmonary Aspergillosis ◽  
P450 Enzyme ◽  
Partial Reversal

ABSTRACT We report a case of accelerated metabolism of voriconazole during therapy for invasive pulmonary aspergillosis, resulting in subtherapeutic levels. Target voriconazole levels were restored with high dosages of voriconazole (up to 40 mg/kg of body weight/day) and the addition of cimetidine as a cytochrome P450 enzyme inhibitor.

Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients

1995 ◽  
Vol 71 (6) ◽  
pp. 287-291 ◽  
Author(s):  
G. F. Behre ◽  
S. Schwartz ◽  
K. Lenz ◽  
W.-D. Ludwig ◽  
H. Wandt ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Amphotericin B ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis
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