scholarly journals Efficacy of UK-109496, a new azole antifungal agent, in an experimental model of invasive aspergillosis.

1996 ◽  
Vol 40 (1) ◽  
pp. 86-91 ◽  
Author(s):  
D George ◽  
P Miniter ◽  
V T Andriole
Keyword(s):  
Body Weight ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Antifungal Agent ◽  
Half Life ◽  
Oral Therapy ◽  
Rabbit Model ◽  
Circulating Antigen ◽  
Liver And Kidney ◽  
Tissue Burden

The efficacy of UK-109496, a new azole antifungal agent, was evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with UK-109496 at a dosage of 10 or 15 mg/kg of body weight every 8 h was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. UK-109496 eliminated mortality and also reduced the tissue burden of Aspergillus fumigatus 10- to 100-fold in liver and kidney tissues and to a lesser degree in lung tissue, and at the higher dose, no viable organisms were recovered from brain tissue from these animals. Both dosages of UK-109496 decreased or eliminated circulating antigen. The half-life of UK-109496 in rabbits was 2.5 to 3 h, and no accumulation of drug was seen even after 15 doses in either uninfected or infected animals. Thus, UK-109496 shows activity in this rabbit model of invasive aspergillosis. Additional studies are needed to determine the potential of the drug for use in the treatment of this infection.

scholarly journals Efficacies of Two New Antifungal Agents, the Triazole Ravuconazole and the Echinocandin LY-303366, in an Experimental Model of Invasive Aspergillosis

2000 ◽  
Vol 44 (12) ◽  
pp. 3381-3388 ◽  
Author(s):  
Jenna Roberts ◽  
Kathleen Schock ◽  
Susan Marino ◽  
Vincent T. Andriole
Keyword(s):  
Body Weight ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Oral Therapy ◽  
Antifungal Agents ◽  
Rabbit Model ◽  
Active Agent ◽  
Aspergillus Antigen

ABSTRACT The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge. Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis. Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues. The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either drug was seen after 6 days of treatment. Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B. Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection.

scholarly journals Efficacy of Albaconazole (UR-9825) in Treatment of Disseminated Scedosporium prolificans Infection in Rabbits

2003 ◽  
Vol 47 (6) ◽  
pp. 1948-1951 ◽  
Author(s):  
Javier Capilla ◽  
Clara Yustes ◽  
Emili Mayayo ◽  
Belkys Fernández ◽  
Montserrat Ortoneda ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Rabbit Model ◽  
Systemic Infection ◽  
Control Group ◽  
Scedosporium Prolificans ◽  
Tissue Burden

ABSTRACT There are no effective therapeutics for treating invasive Scedosporium prolificans infections. Doses of 15, 25, and 50 mg/kg of body weight/day for the new triazole albaconazole (ABC) were evaluated in an immunocompetent rabbit model of systemic infection with this mold. Treatments were begun 1 day after challenge and given for 10 days. ABC at any dose was more effective than amphotericin B (AMB) at 0.8 mg/kg/day at clearing S. prolificans from tissue (P < 0.007). The percentages of survival at 25 mg of ABC/kg/day were similar to those obtained with AMB. Rabbits showed 100% survival when they were treated with 50 mg of ABC per kg (P < 0.0001 versus control group), and only this dosage was able to reduce tissue burden significantly in the five organs studied, i.e., spleen, kidneys, liver, lungs, and brain.

Residues of famphur in bovine tissues and milk following its application as a pour-on insecticide

1976 ◽  
Vol 16 (78) ◽  
pp. 82 ◽  
Author(s):  
AM Annand ◽  
JHP Dingle ◽  
AB Heath ◽  
WA Palmer
Keyword(s):  
Body Weight ◽  
Topical Application ◽  
Half Life ◽  
Subcutaneous Fat ◽  
Maximum Level ◽  
Post Mortem ◽  
The Third ◽  
Whole Milk ◽  
Liver And Kidney ◽  
Residue Levels

Three experiments were conducted to determine residues of famphur in tissues and milk of cattle following its topical application. Subcutaneous fat, sampled by biopsy, from animals treated at 150 mg famphur per kg body weight contained maximum residues of famphur (about 10 mg kg-1, average) one day after treatment. Levels of treatment at 50 mg kg-1 and 25 mg kg-1 yielded similar but lower residues after the same period (2.08 and 1.8 p.p.m, respectively). The half-life of famphur residues was independent of the initial residue levels and was calculated as 0.9 day. Mean residues were negligible (highest mean 0.08 p.p.m.) by five days after treatment. Post-mortem sampling of cattle treated with famphur at 45 mg kg-1 showed that at one day and seven days after treatment, residues in fats (up to 1.25 p.p.m. and 0.53 p.p.m. respectively) and muscle (1.41 p.p.m. and 0.71 p.p.m. respectively) were similar but were higher than the negligible levels (0.05 p.p.m. or less) found in liver and kidney. By 14 days, levels in all tissues were very low (0.11 p.p.m. or less). In milk from cows treated with 23 mg famphur kg-1, 76 per cent of the famphur was found in the butterfat and a maximum level (0.237 p.p.m.) in whole milk was found in the first milking after treatment. Residues were negligible (0.008 p.p.m.) by the third day.

scholarly journals In Vitro Activities at pH 5.0 and pH 7.0 and In Vivo Efficacy of Flucytosine against Aspergillus fumigatus

2008 ◽  
Vol 52 (12) ◽  
pp. 4483-4485 ◽  
Author(s):  
Paul E. Verweij ◽  
Debbie T. A. Te Dorsthorst ◽  
Willem H. P. Janssen ◽  
Jacques F. G. M. Meis ◽  
Johan W. Mouton
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Murine Model ◽  
Antifungal Agent ◽  
In Vivo Efficacy

ABSTRACT The antifungal agent flucytosine was found to be active in vitro against Aspergillus fumigatus isolates when the MIC was determined at pH 5.0 instead of pH 7.0. The in vitro MIC at pH 5.0 corresponded to the in vivo efficacy of flucytosine monotherapy in a murine model of invasive aspergillosis.

scholarly journals Efficacy of 2-(3,4-Dimethyl-2,5-Dihydro-1H-Pyrrole-2-yl)-1-Methylethyl Pentanoate in a Murine Model of Invasive Aspergillosis

2005 ◽  
Vol 49 (10) ◽  
pp. 4365-4367 ◽  
Author(s):  
Rajesh Dabur ◽  
S. K. Diwedi ◽  
V. Yadav ◽  
V. Mishra ◽  
Rambir Singh ◽  
...  
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Murine Model ◽  
Antifungal Compound ◽  
Dose Dependent

ABSTRACT 2-(3,4-Dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, an antifungal compound, was found to be nontoxic to RAW cells up to a concentration of 312.5 μg/ml, whereas amphotericin B was lethal to all cells at 37.5 μg/ml. The treatment of Aspergillus fumigatus-infected mice with a dose of 200.0 mg of compound/kg of body weight increased their survival rate by 60%, with a decrease in CFU in organ tissues. The protection afforded by the compound against experimental aspergillosis was found to be dose dependent.

scholarly journals Activities of Dalbavancin In Vitro and in a Rabbit Model of Experimental Endocarditis Due to Staphylococcus aureus with or without Reduced Susceptibility to Vancomycin and Teicoplanin

2004 ◽  
Vol 48 (3) ◽  
pp. 1061-1064 ◽  
Author(s):  
Agnès Lefort ◽  
Juliette Pavie ◽  
Louis Garry ◽  
Françoise Chau ◽  
Bruno Fantin
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Half Life ◽  
Rabbit Model ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Once Daily ◽  
Elimination Half Life ◽  
Elimination Half

ABSTRACT For the treatment of rabbit endocarditis, dalbavancin given once daily (10 mg/kg of body weight for 4 days) or as a single 40-mg/kg dose was active against Staphylococcus aureus with or without reduced susceptibility to glycopeptides, as expected from its good in vitro activity, even in broth supplemented with 90% serum and given its prolonged elimination half-life.

scholarly journals Anidulafungin in Combination with Amphotericin B against Aspergillus fumigatus

2009 ◽  
Vol 53 (9) ◽  
pp. 4035-4039 ◽  
Author(s):  
Elisabetta Spreghini ◽  
Fiorenza Orlando ◽  
Alfredo Santinelli ◽  
Eleonora Pisa ◽  
Cristian Loretelli ◽  
...  
Keyword(s):  
Body Weight ◽  
Combination Therapy ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Fungal Burden ◽  
Single Drug

ABSTRACT We investigated the effects of anidulafungin alone and in combination with amphotericin B against Aspergillus fumigatus. Indifference was the only type of interaction observed in vitro. Anidulafungin at 1 and 5 mg/kg of body weight/day, amphotericin B at 1 mg/kg/day, and combination therapy prolonged the survival of mice with invasive aspergillosis. Anidulafungin at 5 mg/kg/day, alone and in combination with amphotericin B, reduced the kidney fungal burden. Overall, the combination was not superior to the most active single drug.

scholarly journals In VivoSynergy of Amphotericin B plus Posaconazole in Murine Aspergillosis

2015 ◽  
Vol 60 (1) ◽  
pp. 296-300 ◽  
Author(s):  
Adela Martin-Vicente ◽  
Javier Capilla ◽  
Josep Guarro
Keyword(s):  
Drug Resistance ◽  
Body Weight ◽  
Fungal Infection ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
High Mortality ◽  
Murine Model ◽  
Mortality Rates ◽  
Content Type ◽  
Tissue Burden

ABSTRACTAspergillus fumigatusis the main mold causing invasive fungal infection that shows high mortality rates. Therapeutic failure and the increase in drug resistance make it necessary to explore alternative treatments for this infection. We have evaluated the efficacy of amphotericin B at 0.8 mg/kg or 0.3 mg/kg of body weight combined with 40 mg/kg of posaconazole against threeA. fumigatusisolates in a murine model of disseminated infection. The combination of the polyene and the azole led to a greater increase in survival and a significantly greater reduction in tissue burden than monotherapies.

Turnover and Distribution of 131Iodine-Labelled Human Fibrinogen

1964 ◽  
Vol 11 (02) ◽  
pp. 404-422 ◽  
Author(s):  
Annemarie Amris ◽  
C. J Amris
Keyword(s):  
Body Weight ◽  
Cancer Patient ◽  
Distribution Ratio ◽  
Half Life ◽  
Fibrinolytic Activity ◽  
The Other ◽  
Turnover Rates ◽  
Human Fibrinogen ◽  
Coagulation Defects ◽  
Fractional Turnover

Summary14 patients (5 diabetics with arteriosclerotic complications, 4 patients with thrombo-embolic disease, 4 with cirrhosis, coagulation defects and increased fibrinolytic activity, and 1 cancer patient) and 3 control patients were subjected to turnover studies with 13iodine labelled human fibrinogen.Half-life times in the control patients were found to be 4 days, the fractional turnover rates 19–23 per cent, of intravascular fibrinogen per day, and the absolute turnover 0.02 to 0.06 gm per day per kg. body weight. The other patient’s half-life times and turnover rates varied considerably from 0.9–5.5 days, 13–160 per cent, per day of intravascular fibrinogen and 0.02–0.4 gm per day per kg. body weight respectively.As fibrinogen unlike other proteins subjected to turnover studies, is converted to fibrin, it is not possible to measure the true intra-extravascular distribution ratio of fibrinogen. But intravascular fibrinogen could be approximated to constitute 68–99 per cent, of the total fibrinogen. There is justification in believing that fibrinogen is degradated through a continuous coagulation in equilibrium with fibrinolysis, and that the organism contains a greater mass of fibrin, the “fibrin pool”. Considerations of the turnover mechanism can however only be hypothetical.

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