Comparison of fluconazole and amphotericin B in prophylaxis of experimental Candida endocarditis caused by non-C. albicans strains.

1996 ◽  
Vol 40 (2) ◽  
pp. 494-496 ◽  
Author(s):  
A S Bayer ◽  
M D Witt ◽  
E Kim ◽  
M A Ghannoum
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Dose Regimen ◽  
Prophylactic Efficacy ◽  
Endocarditis Prophylaxis ◽  
Prophylactic Dose ◽  
Candida Strain ◽  
Fungistatic Agent

Amphotericin B (1 mg/kg of body weight, intravenous) and fluconazole (100 mg/kg, intraperitoneal) were compared in the prophylaxis of experimental Candida endocarditis caused by drug-susceptible, non-C. albicans strains C. tropicalis and C. parapsilosis. Neither antifungal agent was effective at preventing endocarditis due to either Candida strain when either agent was administered in a single-dose regimen (1 h prior to fungal challenge); the prophylactic efficacy of both agents increased substantially when a second prophylactic dose was given (24 h postchallenge). The excellent prophylactic efficacy of fluconazole, a fungistatic agent, underscores the importance of microbistatic mechanisms in endocarditis prophylaxis.

scholarly journals Treatment of Murine Fusariosis with SCH 56592

1999 ◽  
Vol 43 (3) ◽  
pp. 589-591 ◽  
Author(s):  
M. Lozano-Chiu ◽  
S. Arikan ◽  
V. L. Paetznick ◽  
E. J. Anaissie ◽  
D. Loebenberg ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Fusarium Solani ◽  
Antifungal Agent ◽  
Systemic Infection ◽  
Immunocompetent Mice ◽  
Systemic Infections ◽  
Organ Clearance

ABSTRACT Doses of 10 to 100 mg of the azole antifungal agent SCH 56592/kg of body weight/day were studied in immunocompetent mice as therapy for systemic infection by Fusarium solani. Treatment was begun 1 h after intravenous infection and continued daily for 4 or 13 doses. Prolongation of survival and organ clearance were dependent on both the dose and the duration of SCH 56592 therapy, with the best results seen at 50 and 100 mg/kg/day. The results at the highest doses of SCH 56592 used (50 or 100 mg/kg/day) were comparable to those obtained with amphotericin B at 1 mg/kg/day. SCH 56592 has potential for therapy of systemic infections caused byF. solani.

scholarly journals Pharmacokinetics and Buccal Mucosal Concentrations of a 15 Milligram per Kilogram of Body Weight Total Dose of Liposomal Amphotericin B Administered as a Single Dose (15 mg/kg), Weekly Dose (7.5 mg/kg), or Daily Dose (1 mg/kg) in Peripheral Stem Cell Transplant Patients

2009 ◽  
Vol 53 (9) ◽  
pp. 3664-3674 ◽  
Author(s):  
Paul O. Gubbins ◽  
Jarrett R. Amsden ◽  
Scott A. McConnell ◽  
Elias J. Anaissie
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Single Dose ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Stem Cell Transplant ◽  
Plasma Concentrations ◽  
Cell Transplant ◽  
Mucosal Tissue ◽  
Tissue Concentrations

ABSTRACT The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n = 2) or significant increases in the serum creatinine (Scr) levels (n = 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 μg/ml for the first 7 days and >0.220 μg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 μg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K+, Mg2+, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB.

scholarly journals Superior Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in the Treatment of Severe Candidiasis in Leukopenic Mice

1998 ◽  
Vol 42 (9) ◽  
pp. 2431-2433 ◽  
Author(s):  
Els W. M. van Etten ◽  
Susan V. Snijders ◽  
Wim van Vianen ◽  
Irma A. J. M. Bakker-Woudenberg
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Single Dose ◽  
Polyethylene Glycol ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Low Dose ◽  
Systemic Candidiasis ◽  
Superior Efficacy ◽  
Single Dose Treatment

ABSTRACT In leukopenic mice with severe systemic candidiasis, single-dose treatment (5 mg of amphotericin B [AMB]/kg of body weight) with long-circulating polyethylene glycol-coated AMB liposomes (PEG-AMB-LIP) resulted in zero mortality and a significant reduction in the number of viable Candida albicans in the kidney, whereas 70% mortality was seen in mice treated with five daily doses of AmBisome (5 mg of AMB/kg · day). When the first of five daily doses of AmBisome was combined with a single low dose of Fungizone (0.1 mg of AMB/kg), the efficacy was equal to that of PEG-AMB-LIP.

scholarly journals Single-Dose AmBisome (Liposomal Amphotericin B) as Prophylaxis for Murine Systemic Candidiasis and Histoplasmosis

2000 ◽  
Vol 44 (9) ◽  
pp. 2327-2332 ◽  
Author(s):  
April Garcia ◽  
Jill P. Adler-Moore ◽  
Richard T. Proffitt
Keyword(s):  
Single Dose ◽  
Amphotericin B ◽  
Histoplasma Capsulatum ◽  
Fungal Growth ◽  
Parent Drug ◽  
Control Group ◽  
High Dose ◽  
Prophylactic Efficacy ◽  
Immunocompetent Mice ◽  
Immunosuppressed Mice

ABSTRACT AmBisome is a liposomal formulation of amphotericin B that has broad-spectrum antifungal activity and greatly reduced toxicity compared to the parent drug. In this study, amphotericin B deoxycholate (Fungizone) (1 mg/kg) and AmBisome (1 to 20 mg/kg) were tested as single-dose prophylactic agents in both immunocompetent and immunosuppressed C57BL/6 mice challenged with either Candida albicans or Histoplasma capsulatum. Prophylactic efficacy was based on survival and fungal burden in the target organ (kidneys or spleen). At 9 to 10 days after histoplasma challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the control and Fungizone groups had died. All AmBisome-treated mice survived, although in the AmBisome groups given 1 mg/kg, the mice became moribund by day 10 to 12. No spleen CFU were detected in the histoplasma-challenged mice given 10 or 20 mg of AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal growth and/or death had occurred in all immunosuppressed mice except for four mice receiving 20 mg of AmBisome per kg. There were still no detectable fungi in the spleens of immunocompetent mice given 10 or 20 mg of AmBisome per kg. In the C. albicans experiment at 7 days postchallenge, all animals in both untreated and treated groups were alive with culture-positive kidneys. The kidney fungal burdens in AmBisome groups given 5 to 20 mg/kg were at least 1 log unit lower than those in the Fungizone group and significantly lower than those in the untreated control group (P < 0.05). There was a trend toward decreasing fungal growth in the kidneys as the dose of AmBisome was increased. In conclusion, these results show that a single high dose of AmBisome (5 to 20 mg/kg) had prophylactic efficacy in immunocompetent and immunosuppressed murine H. capsulatum and C. albicans models.

scholarly journals In Vitro and In Vivo Activities of CS-758 (R-120758), a New Triazole Antifungal Agent

2002 ◽  
Vol 46 (2) ◽  
pp. 367-370 ◽  
Author(s):  
Yasuki Kamai ◽  
Tamako Harasaki ◽  
Takashi Fukuoka ◽  
Satoshi Ohya ◽  
Katsuhisa Uchida ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
The Other ◽  
In Vitro Activity ◽  
Effective Doses ◽  
Low Levels ◽  
Systemic Infections

ABSTRACT The activity of CS-758 (R-120758), a new triazole antifungal agent, was evaluated and compared with those of fluconazole, itraconazole, and amphotericin B in vitro and with those of fluconazole and itraconazole in vivo. CS-758 exhibited potent in vitro activity against clinically important fungi. The activity of CS-758 against Candida spp. was superior to that of fluconazole and comparable or superior to those of itraconazole and amphotericin B. CS-758 retained potent activity against Candida albicans strains with low levels of susceptibility to fluconazole (fluconazole MIC, 4 to 32 μg/ml). Against Aspergillus spp. and Cryptococcus neoformans, the activity of CS-758 was at least fourfold superior to those of the other drugs tested. CS-758 also exhibited potent in vivo activity against murine systemic infections caused by C. albicans, C. neoformans, Aspergillus fumigatus, and Aspergillus flavus. The 50% effective doses against these infections were 0.41 to 5.0 mg/kg of body weight. These results suggest that CS-758 may be useful in the treatment of candidiasis, cryptococcosis, and aspergillosis.

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.

Experimental Venous Thrombosis in Rats

1963 ◽  
Vol 09 (02) ◽  
pp. 427-435 ◽  
Author(s):  
Arne Nordöy
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Single Dose ◽  
Jugular Vein ◽  
Methanol Solution ◽  
Fibrinogen Concentration ◽  
Moderate Increase ◽  
Slight Effect ◽  
Plasma Coagulation ◽  
Global Tests

Summary1. Thrombosis in rats were produced by Blake et al.’s technique of application of formalin solution to the jugular vein. The incidence of thrombosis produced by a 10% (v/v) formalin in 65% methanol solution and observed after 24 hours was 30% ± 4.6 S. D.2. The administration of 100 mg EACA 1,000 g body weight orally every fourth hour for 24 hours increased the incidence of thrombosis about twice (to about 65%).A single dose of 400 mg EACA 1,000 g body weight had a slight effect only.3. EACA increased markedly the antifibrinolytic activity in plasma with a maximum after 3—5 hours oral administration. A moderate increase in the fibrinogen concentration was observed in all groups.4. Global tests for plasma coagulation, the platelet count and the number of adhesive platelets were not significantly influenced by the administration of EACA.

Potential anti-toxic effect of d-ribose-l-cysteine supplement on the reproductive functions of male rats administered cyclophosphamide

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gabriel O. Oludare ◽  
Gbenga O. Afolayan ◽  
Ganbotei G. Semidara
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Sperm Motility ◽  
Sperm Count ◽  
Male Rats ◽  
Oxidative Enzymes ◽  
Protective Effects ◽  
Testosterone Levels ◽  
Group I ◽  
Antioxidant Defence System

Abstract Objectives This study aimed to access the protective effects of d-ribose-l-cysteine (DRLC) on cyclophosphamide (CPA) induced gonadal toxicity in male rats. Methods Forty-eight male Sprague-Dawley rats were divided into six groups of eight rats each. Group I the control, received distilled water (10 ml/kg), Group II received a single dose of CPA 100 mg/kg body weight intraperitoneally (i.p), Groups III and IV received a single dose of CPA at 100 mg/kg (i.p) and then were treated with DRLC at 200 mg/kg bodyweight (b.w) and 400 mg/kg b.w for 10 days, respectively. Rats in Groups V and VI received DRLC at 200 and 400 mg/kg b.w for 10 days, respectively. DRLC was administered orally. Results Results showed that CPA increased percentage of abnormal sperm cells and reduced body weight, sperm count, sperm motility, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels (p<0.05). CPA also induced oxidative stress as indicated by the increased malondialdehyde (MDA) content and reduced activities of the oxidative enzymes measured (p<0.05). Liver enzymes were elevated while the blood cells production was decreased in the rats administered CPA. DRLC supplementation enhanced the antioxidant defence system as indicated in the reduced MDA levels and increased activities of the antioxidant enzymes when compared with CPA (p<0.05). Bodyweight, sperm count, sperm motility, FSH, and testosterone levels were increased in the CPA + DRLC II group compared with CPA (p<0.05). Conclusions The results of this present study showed that DRLC has a potential protective effect on CPA-induced gonadotoxicity.

scholarly journals Extended single-dose toxicity study of [211At]NaAt in mice for the first-in-human clinical trial of targeted alpha therapy for differentiated thyroid cancer

2021 ◽  
Author(s):  
Tadashi Watabe ◽  
Kazuko Kaneda-Nakashima ◽  
Kazuhiro Ooe ◽  
Yuwei Liu ◽  
Kenta Kurimoto ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Thyroid Cancer ◽  
Single Dose ◽  
General Condition ◽  
Blood Test ◽  
Differentiated Thyroid Cancer ◽  
Targeted Alpha Therapy ◽  
Evaluation Point ◽  
Alpha Therapy

Abstract Objective Astatine (211At) is a promising alpha emitter as an alternative to iodine (131I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of [211At]NaAt to determine the FIH dose. Methods [211At]NaAt solution was injected into normal 6-week-old mice (male (n = 50) and female (n = 50), body weight: male 33.2 ± 1.7 g, female 27.3 ± 1.5 g), which were then divided into four groups: 5 MBq/kg (n = 20), 20 MBq/kg (n = 20), 50 MBq/kg (n = 30), saline control (n = 30). The mice were followed up for 5 days (primary evaluation point for acute toxicity: n = 80) or 14 days (n = 20: evaluation point for recovery) to monitor general condition and body weight change. At the end of the observation period, necropsy, blood test, organ weight measurement, and histopathological examination were performed. For body weight, blood test, and organ weight, statistical analyses were performed to compare data between the control and injected groups. Results No abnormal findings were observed in the general condition of mice. In the 50 MBq/kg group, males (days 3 and 5) showed a significant decrease in body weight compared with the control. However, necropsy did not differ significantly beyond the range of spontaneous lesions. In the blood test, males (50 MBq/kg) and females (50 MBq/kg) showed a decrease in white blood cell and platelet counts on day 5, and recovery on day 14. In the testis, a considerable weight decrease was observed on day 14 (50 MBq/kg), and multinucleated giant cells were observed in all mice, indicating a significant change related to the administration of [211At]NaAt. Conclusions In the extended single-dose toxicity study of [211At]NaAt, administration of high doses resulted in weight loss, transient bone marrow suppression, and pathological changes in the testis, which require consideration in the FIH clinical trial.

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