The Experts below are selected from a list of 2262 Experts worldwide ranked by ideXlab platform
Urs Schanz - One of the best experts on this subject based on the ideXlab platform.
-
continuously infused <B>AmphotericinB> B Deoxycholate for primary treatment of invasive fungal disease in acute myeloid leukaemia
Hematological Oncology, 2018Co-Authors: Christoph Rothenbuhler, Ulrike Held, Markus G Manz, Urs Schanz, Bernhard GerberAbstract:Continuous administration of <B>AmphotericinB> B Deoxycholate over 24 hours (24 h-D-AmB) is Better tolerated than rapid infusions. However, toxicity and outcome have not Been assessed in a homogenous patient population with acute myeloid leukaemia (AML). We retrospectively analysed renal function and outcome in all adult patients with AML undergoing intensive chemotherapy Between 2007 and 2012 at our institution. We compared a patient group with exposure to 24 h-D-AmB to a patient group without exposure to 24 h-D-AmB. One hundred and eighty-one consecutive patients were analysed, 133 (73.5%) received at least 1 dose of 24 h-D-AmB, and 48 (26.5%) did not. Reasons for 24 h-D-AmB initiation were invasive fungal disease (IFD) in 63.5% and empirical treatment for feBrile neutropenia in 36.5% of the cases. Most patients with IFD received an oral triazole drug at hospital discharge. Baseline characteristics were well matched. <B>AmphotericinB> B Deoxycholate over 24 hours was given for a median 7 days (interquartile range 3-13). Peak creatinine concentration was higher in the 24 h-D-AmB-group (104.5 vs. 76 μmol/L, P < .001) But normalized within 1 month after therapy (65.5 vs. 65 μmol/L, P = .979). In neither of the 2 groups, end-stage renal disease occurred. There was no difference in 60-day survival (90% vs. 90%) and 2-year survival (58% vs. 58%). Invasive fungal disease partial response or Better was oBserved in 68% of the patients. We conclude that antifungal therapy with continuously infused <B>AmphotericinB> B Deoxycholate is safe in patients with AML. An antiinfective strategy Based on 24 h-D-AmB in first line followed By an oral triazole compound represents an economically attractive treatment option.
-
Continuously infused <B>AmphotericinB> B Deoxycholate for primary treatment of invasive fungal disease in acute myeloid leukaemia.
Hematological oncology, 2018Co-Authors: Christoph Rothenbuhler, Ulrike Held, Markus G Manz, Urs Schanz, Bernhard GerberAbstract:Continuous administration of <B>AmphotericinB> B Deoxycholate over 24 hours (24 h-D-AmB) is Better tolerated than rapid infusions. However, toxicity and outcome have not Been assessed in a homogenous patient population with acute myeloid leukaemia (AML). We retrospectively analysed renal function and outcome in all adult patients with AML undergoing intensive chemotherapy Between 2007 and 2012 at our institution. We compared a patient group with exposure to 24 h-D-AmB to a patient group without exposure to 24 h-D-AmB. One hundred and eighty-one consecutive patients were analysed, 133 (73.5%) received at least 1 dose of 24 h-D-AmB, and 48 (26.5%) did not. Reasons for 24 h-D-AmB initiation were invasive fungal disease (IFD) in 63.5% and empirical treatment for feBrile neutropenia in 36.5% of the cases. Most patients with IFD received an oral triazole drug at hospital discharge. Baseline characteristics were well matched. <B>AmphotericinB> B Deoxycholate over 24 hours was given for a median 7 days (interquartile range 3-13). Peak creatinine concentration was higher in the 24 h-D-AmB-group (104.5 vs. 76 μmol/L, P
-
Nephrotoxicity of cyclosporine A and <B>AmphotericinB> B-Deoxycholate as continuous infusion in allogenic stem cell transplantation.
Swiss medical weekly, 2002Co-Authors: Katrin Furrer, Alexander Imhof, Andreas Schaffner, Stephan R Vavricka, Joerg Halter, Urs SchanzAbstract:Nephrotoxicity is an important side effect of amphothericin B Deoxycholate (ampho B) and cyclosporine A (CsA). The comBined administration of these drugs is frequent in patients with haematological diseases undergoing allogeneic stem cell transplantation. To assess the additional renal toxicity of ampho B given as a continuous infusion in addition to CsA. In a retrospective study renal function was investigated in patients receiving CsA alone or in comBination with ampho B (24-hour infusion) after allogeneic stem cell transplantation Between January 1998 and April 2001. Of a total of 84 patients, 22 were treated with ampho B. There was a statistically significant decline in renal function in comparison to the 62 patients receiving CsA alone. However, renal insufficiency in all patients remained in a clinically acceptaBle range and was reversiBle. The residual renal dysfunction at the end of the hospitalisation was mainly due to continuing therapy with CsA. <B>AmphotericinB> B Deoxycholate in addition to CsA leads to a statistically significant But clinically toleraBle worsening of renal function. Using a 24-hour infusion and strict salt repletion, <B>AmphotericinB> B can Be administered safely as Deoxycholate in Bone marrow transplant patients in conjunction with CsA for proven or suspected fungal infections.
-
Nephrotoxicity of cyclosporine A and <B>AmphotericinB> B-Deoxycholate as continuous infusion in allogenic stem cell transplantation.
Swiss Medical Weekly, 2002Co-Authors: Katrin Furrer, Alexander Imhof, Andreas Schaffner, Vavricka, Jörg Halter, Urs SchanzAbstract:Background Nephrotoxicity is an important side effect of amphothericin B Deoxycholate (ampho B) and cyclosporine A (CsA). The comBined administration of these drugs is frequent in patients with haematological diseases undergoing allogeneic stem cell transplantation. Aim To assess the additional renal toxicity of ampho B given as a continuous infusion in addition to CsA. Methods In a retrospective study renal function was investigated in patients receiving CsA alone or in comBination with ampho B (24-hour infusion) after allogeneic stem cell transplantation Between January 1998 and April 2001. Results Of a total of 84 patients, 22 were treated with ampho B. There was a statistically significant decline in renal function in comparison to the 62 patients receiving CsA alone. However, renal insufficiency in all patients remained in a clinically acceptaBle range and was reversiBle. The residual renal dysfunction at the end of the hospitalisation was mainly due to continuing therapy with CsA. Conclusion <B>AmphotericinB> B Deoxycholate in addition to CsA leads to a statistically significant But clinically toleraBle worsening of renal function. Using a 24-hour infusion and strict salt repletion, <B>AmphotericinB> B can Be administered safely as Deoxycholate in Bone marrow transplant patients in conjunction with CsA for proven or suspected fungal infections.
William W. Hope - One of the best experts on this subject based on the ideXlab platform.
-
Population Pharmacodynamics of <B>AmphotericinB> B Deoxycholate for Disseminated Infection Caused By Talaromyces marneffei.
Antimicrobial agents and chemotherapy, 2018Co-Authors: Nguyen Thi Mai Thu, John R. Perfect, Ashley Nguyen, Nguyen Tat Thanh, Nguyen Van Vinh Chau, Guy E. Thwaites, Ruwanthi Kolamunnage-dona, William W. HopeAbstract:<B>AmphotericinB> B Deoxycholate (DAmB) is a first-line agent for the initial treatment of talaromycosis. However, little is known aBout the population pharmacokinetics and pharmacodynamics of DAmB for talaromycosis. Pharmacokinetic data were oBtained from 78 patients; among them, 55 patients had serial fungal CFU counts in Blood also availaBle for analysis. A population pharmacokinetic-pharmacodynamic model was fitted to the data. The relationships Between the area under the concentration-time curve (AUC)/MIC and the time to Blood culture sterilization and the time to death were investigated. There was only modest pharmacokinetic variaBility in the average AUC, with a mean ± standard deviation of 11.51 ± 3.39 mg·h/liter. The maximal rate of drug-induced kill was 0.133 log10 CFU/ml/h, and the plasma concentration of the DAmB that induced the half-maximal rate of kill was 0.02 mg/liter. Fifty percent of patients sterilized their Bloodstreams By 83.16 h (range, 13 to 264 h). A higher initial fungal Burden was associated with a longer time to sterilization (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.36 to 0.70; P
-
population pharmacodynamics of <B>AmphotericinB> B Deoxycholate for disseminated infection caused By talaromyces marneffei
Antimicrobial Agents and Chemotherapy, 2018Co-Authors: Nguyen Thi Mai Thu, John R. Perfect, Ashley Nguyen, Nguyen Tat Thanh, Nguyen Van Vinh Chau, Guy E. Thwaites, Ruwanthi Kolamunnagedona, William W. HopeAbstract:<B>AmphotericinB> B Deoxycholate (DAmB) is a first-line agent for the initial treatment of talaromycosis. However, little is known aBout the population pharmacokinetics and pharmacodynamics of DAmB for talaromycosis. Pharmacokinetic data were oBtained from 78 patients; among them, 55 patients had serial fungal CFU counts in Blood also availaBle for analysis. A population pharmacokinetic-pharmacodynamic model was fitted to the data. The relationships Between the area under the concentration-time curve (AUC)/MIC and the time to Blood culture sterilization and the time to death were investigated. There was only modest pharmacokinetic variaBility in the average AUC, with a mean ± standard deviation of 11.51 ± 3.39 mg·h/liter. The maximal rate of drug-induced kill was 0.133 log10 CFU/ml/h, and the plasma concentration of the DAmB that induced the half-maximal rate of kill was 0.02 mg/liter. Fifty percent of patients sterilized their Bloodstreams By 83.16 h (range, 13 to 264 h). A higher initial fungal Burden was associated with a longer time to sterilization (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.36 to 0.70; P < 0.001). There was a weak relationship Between AUC/MIC and the time to sterilization, although this did not reach statistical significance (HR, 1.03; 95% CI, 1.00 to 1.06, P = 0.091). Furthermore, there was no relationship Between the AUC/MIC and time to death (HR, 0.97; 95% CI, 0.88 to 1.08; P = 0.607) or early fungicidal activity {slope = log[(0.500 - 0.003·(AUC/MIC)]; P = 0.319} adjusted for the initial fungal Burden. The population pharmacokinetics of DAmB are surprisingly consistent. The time to sterilization of the Bloodstream may Be a useful pharmacodynamic endpoint for future studies. (This study has Been registered at the ISRCTN registry under no. ISRCTN59144167.).
-
Population Pharmacokinetic Model and Meta-analysis of Outcomes of <B>AmphotericinB> B Deoxycholate Use in Adults with Cryptococcal Meningitis.
Antimicrobial agents and chemotherapy, 2018Co-Authors: Katharine E. Stott, William W. Hope, Ruwanthi Kolamunnage-dona, Fm Kibengo, Justin Beardsley, Sarah Whalley, Nguyen Thi Hoang Mai, Nguyễn Lê Nhu’ Tùng, Ngo Thi Kim Cuc, Jeremy N. DayAbstract:There is a limited understanding of the population pharmacokinetics (PK) and pharmacodynamics (PD) of <B>AmphotericinB> B Deoxycholate (DAmB) for cryptococcal meningitis. A PK study was conducted in n = 42 patients receiving DAmB (1 mg/kg of Body weight every 24 h [q24h]). A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of treatment of cryptococcal meningitis patients with DAmB monotherapy, and a meta-analysis was performed. The PK parameter means (standard deviations) were as follows: clearance, 0.03 (0.01) × weight + 0.67 (0.01) liters/h; volume, 0.82 (0.80) × weight + 1.76 (1.29) liters; first-order rate constant from central compartment to peripheral compartment, 5.36 (6.67) h-1; first-order rate constant from peripheral compartment to central compartment, 9.92 (12.27) h-1 The meta-analysis suggested that the DAmB dosage explained most of the heterogeneity in cereBrospinal fluid (CSF) sterility outcomes But not in mortality outcomes. Simulations of values corresponding to the area under concentration-time curve from h 144 to h 168 (AUC144-168) resulted in median (interquartile range) values of 5.83 mg · h/liter (4.66 to 8.55), 10.16 mg · h/liter (8.07 to 14.55), and 14.51 mg · h/liter (11.48 to 20.42) with dosages of 0.4, 0.7, and 1.0 mg/kg q24h, respectively. DAmB PK is descriBed adequately By a linear model that incorporates weight with clearance and volume. Interpatient PK variaBility is modest and unlikely to Be responsiBle for variaBility in clinical outcomes. There is discordance Between the impact that drug exposure has on CSF sterility and its impact on mortality outcomes, which may Be due to cereBral pathology not reflected in CSF fungal Burden, in addition to clinical variaBles.
-
Pharmacodynamics of <B>AmphotericinB> B Deoxycholate, <B>AmphotericinB> B Lipid Complex, and Liposomal <B>AmphotericinB> B against Aspergillus fumigatus
Antimicrobial agents and chemotherapy, 2015Co-Authors: Zaid Al-nakeeb, Joanne Goodwin, Thomas J. Walsh, Vidmantas Petraitis, Ruta Petraitiene, William W. HopeAbstract:<B>AmphotericinB> B is a first-line agent for the treatment of invasive aspergillosis. However, relatively little is known aBout the pharmacodynamics of <B>AmphotericinB> B for invasive pulmonary aspergillosis. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of <B>AmphotericinB> B Deoxycholate (DAMB), <B>AmphotericinB> B lipid complex (ABLC), and liposomal <B>AmphotericinB> B (LAMB) By using a neutropenic-raBBit model of invasive pulmonary aspergillosis. The study endpoints were lung weight, infarct score, and levels of circulating galactomannan and (1 → 3)-β-D-glucan. Mathematical models were used to descriBe PK-PD relationships. The experimental findings were Bridged to humans By Monte Carlo simulation. Each <B>AmphotericinB> B formulation induced a dose-dependent decline in study endpoints. Near-maximal antifungal activity was evident with DAMB at 1 mg/kg/day and ABLC and LAMB at 5 mg/kg/day. The Bridging study suggested that the "average" patient receiving LAMB at 3 mg/kg/day was predicted to have complete suppression of galactomannan and (1 → 3)-β-D-glucan levels, But 20 to 30% of the patients still had a galactomannan index of >1 and (1 → 3)-β-D-glucan levels of >60 pg/ml. All formulations of <B>AmphotericinB> B induce a dose-dependent reduction in markers of lung injury and circulating fungus-related Biomarkers. A clinical dosage of liposomal <B>AmphotericinB> B of 3 mg/kg/day is predicted to cause complete suppression of galactomannan and (1 → 3)-β-D-glucan levels in the majority of patients.
-
Pharmacokinetics and pharmacodynamics of <B>AmphotericinB> B Deoxycholate, liposomal <B>AmphotericinB> B, and <B>AmphotericinB> B lipid complex in an in vitro model of invasive pulmonary aspergillosis
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Jodi M Lestner, Jayesh Majithiya, Gerard M. Jensen, Lea Gregson, Susan J Howard, Joanne Goodwin, Thomas J. Walsh, William W. HopeAbstract:The pharmacodynamic and pharmacokinetic (PK-PD) properties of <B>AmphotericinB> B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an in vitro model of IPA to further elucidate the PK-PD of <B>AmphotericinB> B Deoxycholate (DAmB), liposomal <B>AmphotericinB> B (LAmB) and <B>AmphotericinB> B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated. Pharmacodynamic relationships were defined By measuring concentrations of galactomannan in endovascular and alveolar compartments. Confocal microscopy was used to visualize fungal Biomass. A mathematical model was used to calculate the area under the concentration-time curve (AUC) in each compartment and estimate the extent of drug penetration. The interaction of LAmB with host cells and hyphae was visualized using sulforhodamine B-laBeled liposomes. The MICs for the pure compound and the three formulations were comparaBle (0.125 to 0.25 mg/liter). For all formulations, concentrations of AmB progressively declined in the endovascular fluid as the drug distriButed into the cellular Bilayer. Depending on the formulation, the AUCs for AmB were 10 to 300 times higher within the cells than within endovascular fluid. The concentrations producing a 50% maximal effect (EC50) in the endovascular compartment were 0.12, 1.03, and 4.41 mg/liter for DAmB, LAmB, and ABLC, respectively, whereas, the EC50 in the alveolar compartment were 0.17, 7.76, and 39.34 mg/liter, respectively. Confocal microscopy suggested that liposomes interacted directly with hyphae and host cells. The PK-PD relationships of the three most widely used formulations of AmB differ markedly within an in vitro lung model of IPA.
Alexander Imhof - One of the best experts on this subject based on the ideXlab platform.
-
Treatment options of invasive fungal infections in adults.
Swiss medical weekly, 2006Co-Authors: Ursula Flückiger, Jorge Garbino, Alexander Imhof, Oscar Marchetti, Jacques Bille, Philippe Eggimann, Stefan Zimmerli, Christian Ruef, Didier Pittet, Martin TäuberAbstract:A panel of infectious disease specialists, clinical microBiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida Bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. <B>AmphotericinB> B Deoxycholate or caspofungin would Be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with <B>AmphotericinB> B Deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microBiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. alBicans, C. tropicalis or C. parapsilosis. When infections are caused By C. glaBrata or By C. krusei, caspofungin or <B>AmphotericinB> B Deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and comBination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal <B>AmphotericinB> B are recommended for salvage therapy for refractory disease. ComBination therapy with caspofungin plus voriconazole or liposomal <B>AmphotericinB> B should Be considered in critically ill patients. <B>AmphotericinB> B Deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.
-
Continuous Infusion of Escalated Doses of <B>AmphotericinB> B Deoxycholate: An Open-LaBel OBservational Study
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2003Co-Authors: Alexander Imhof, Roland B. Walter, Andreas SchaffnerAbstract:<B>AmphotericinB> B Deoxycholate (AmB-d) remains a mainstay of antifungal therapy for immunocompromised patients, despite Being associated with significant therapy-related toxicity. Because continuous infusion of AmB-d is Better tolerated than traditional administration over 2-6 hours, we evaluated escalation of the AmB-d dose in 33 patients (31 of whom were neutropenic), for whom the initial dosage of AmB-d (1 mg/kg/ day) was gradually increased to 2.0 mg/kg/day when renal function remained staBle and the drug was tolerated. Dose escalation was possiBle without delay in 28 patients. Median duration of AmB-d therapy was 16 days (range, 7-72 days). Infusion-related reactions accompanied 2-fold decrease in creatine clearance was oBserved in 5 patients, and the decrease was dose-limiting in only 1 patient; no dialysis was required. In conclusion, continuous infusion of AmB-d escalated to 2.0 mg/kg/day seems not to cause additional impairment of vital organ functions and to Be well tolerated By most patients.
-
Nephrotoxicity of cyclosporine A and <B>AmphotericinB> B-Deoxycholate as continuous infusion in allogenic stem cell transplantation.
Swiss medical weekly, 2002Co-Authors: Katrin Furrer, Alexander Imhof, Andreas Schaffner, Stephan R Vavricka, Joerg Halter, Urs SchanzAbstract:Nephrotoxicity is an important side effect of amphothericin B Deoxycholate (ampho B) and cyclosporine A (CsA). The comBined administration of these drugs is frequent in patients with haematological diseases undergoing allogeneic stem cell transplantation. To assess the additional renal toxicity of ampho B given as a continuous infusion in addition to CsA. In a retrospective study renal function was investigated in patients receiving CsA alone or in comBination with ampho B (24-hour infusion) after allogeneic stem cell transplantation Between January 1998 and April 2001. Of a total of 84 patients, 22 were treated with ampho B. There was a statistically significant decline in renal function in comparison to the 62 patients receiving CsA alone. However, renal insufficiency in all patients remained in a clinically acceptaBle range and was reversiBle. The residual renal dysfunction at the end of the hospitalisation was mainly due to continuing therapy with CsA. <B>AmphotericinB> B Deoxycholate in addition to CsA leads to a statistically significant But clinically toleraBle worsening of renal function. Using a 24-hour infusion and strict salt repletion, <B>AmphotericinB> B can Be administered safely as Deoxycholate in Bone marrow transplant patients in conjunction with CsA for proven or suspected fungal infections.
-
Nephrotoxicity of cyclosporine A and <B>AmphotericinB> B-Deoxycholate as continuous infusion in allogenic stem cell transplantation.
Swiss Medical Weekly, 2002Co-Authors: Katrin Furrer, Alexander Imhof, Andreas Schaffner, Vavricka, Jörg Halter, Urs SchanzAbstract:Background Nephrotoxicity is an important side effect of amphothericin B Deoxycholate (ampho B) and cyclosporine A (CsA). The comBined administration of these drugs is frequent in patients with haematological diseases undergoing allogeneic stem cell transplantation. Aim To assess the additional renal toxicity of ampho B given as a continuous infusion in addition to CsA. Methods In a retrospective study renal function was investigated in patients receiving CsA alone or in comBination with ampho B (24-hour infusion) after allogeneic stem cell transplantation Between January 1998 and April 2001. Results Of a total of 84 patients, 22 were treated with ampho B. There was a statistically significant decline in renal function in comparison to the 62 patients receiving CsA alone. However, renal insufficiency in all patients remained in a clinically acceptaBle range and was reversiBle. The residual renal dysfunction at the end of the hospitalisation was mainly due to continuing therapy with CsA. Conclusion <B>AmphotericinB> B Deoxycholate in addition to CsA leads to a statistically significant But clinically toleraBle worsening of renal function. Using a 24-hour infusion and strict salt repletion, <B>AmphotericinB> B can Be administered safely as Deoxycholate in Bone marrow transplant patients in conjunction with CsA for proven or suspected fungal infections.
Shyam Sundar - One of the best experts on this subject based on the ideXlab platform.
-
Single-Dose Liposomal <B>AmphotericinB> B for Visceral Leishmaniasis in India
The New England journal of medicine, 2010Co-Authors: Shyam Sundar, Madhukar Rai, Jaya Chakravarty, Henry W MurrayAbstract:Background Some 50% of patients with visceral leishmaniasis (kala-azar) worldwide live in the Indian state of Bihar. Liposomal <B>AmphotericinB> B is an effective treatment when administered in short courses. We wanted to determine whether the efficacy of a single infusion of liposomal <B>AmphotericinB> B was inferior to conventional parenteral therapy, consisting of 15 alternate-day infusions of <B>AmphotericinB> B Deoxycholate. Methods In this open-laBel study, we randomly assigned 412 patients in a 3:1 ratio to receive either liposomal <B>AmphotericinB> B (liposomal-therapy group) or <B>AmphotericinB> B Deoxycholate (conventional-therapy group). Liposomal <B>AmphotericinB> B (at a dose of 10 mg per kilogram of Body weight) was given once, and patients were discharged home 24 hours later. <B>AmphotericinB> B Deoxycholate, which was administered in 15 infusions of 1 mg per kilogram, was given every other day during a 29-day hospitalization. We determined the cure rate 6 months after treatment. Results A total of 410 patients — 304 of 304 patients (100%) in the liposomal-therapy group and 106 of 108 patients (98%) in the conventional-therapy group — had apparent cure responses at day 30. Cure rates at 6 months were similar in the two groups: 95.7% (95% confidence interval [CI], 93.4 to 97.9) in the liposomal-therapy group and 96.3% (95% CI, 92.6 to 99.9) in the conventional-therapy group. Adverse events in the liposomal-therapy group were infusion-related fever or rigors (in 40%) and increased anemia or thromBocytopenia (in 2%); such events in the conventional-therapy group were fever or rigors (in 64%), increased anemia (in 19%), and hypokalemia (in 2%). Nephrotoxicity or hepatotoxicity developed in no more than 1% of patients in each group. Conclusions A single infusion of liposomal <B>AmphotericinB> B was not inferior to and was less expensive than conventional therapy with <B>AmphotericinB> B Deoxycholate. (ClinicalTrials.gov numBer, NCT00628719.)
-
Antileishmanial activity of nano-<B>AmphotericinB> B Deoxycholate
The Journal of antimicrobial chemotherapy, 2008Co-Authors: Krishna Das Manandhar, Thakur Prasad Yadav, Vijay Kumar Prajapati, Subodh Kumar, Madhukar Rai, Anuradha Dube, O.n. Srivastava, Shyam SundarAbstract:OBjectives: The aim of the present study was to compare the efficacy of a nano form of <B>AmphotericinB> B Deoxycholate with that of conventional <B>AmphotericinB> B Deoxycholate for the treatment of visceral leishmaniasis. Methods: We have formulated nanoparticles (10‐20 nM) from <B>AmphotericinB> B Deoxycholate (1‐2 mM) By applying high-pressure (150 argon) milling homogenization and have tested their efficacy in a J774A cell line and in hamsters. Parasite survival and tissue Burden in spleen were evaluated for nano<B>AmphotericinB> B and conventional <B>AmphotericinB> B. Both nano-<B>AmphotericinB> B and conventional <B>AmphotericinB> B were injected intraperitoneally at 5 mg/kg per day for 5 days. Results: The inhiBition of amastigotes in the splenic tissue with nano-<B>AmphotericinB> B was significantly more than with conventional <B>AmphotericinB> B (92.18% versus 74.57%, P 5 0.005). Similarly, the suppression of parasite replication in the spleen was also found to Be significant (99.18% versus 97.17%, P 5 0.05). In a cytotoxicity test, nano-<B>AmphotericinB> B against the J774A cell line had a CC50 of 12.67 mg/L in comparison with 10.61 mg/L for <B>AmphotericinB> B, far higher than the doses used for ED50. Conclusions: Nanoparticles of <B>AmphotericinB> B had significantly greater efficacy than conventional <B>AmphotericinB> B. This formulation may have a favouraBle safety profile, and if production costs are low, it may prove to Be a feasiBle alternative to conventional <B>AmphotericinB> B.
-
<B>AmphotericinB> B treatment for indian visceral leishmaniasis conventional versus lipid formulations
Clinical Infectious Diseases, 2004Co-Authors: Shyam Sundar, H Mehta, A V Suresh, Shri Singh, Rai Madhukar, Henry W MurrayAbstract:In Bihar India where visceral leishmaniasis is hyperendemic <B>AmphotericinB> B Deoxycholate is now first-line parenteral treatment. To test the efficacy of <B>AmphotericinB> B Deoxycholate versus that of its lipid formulations Indian patients were randomized to receive treatment with <B>AmphotericinB> B Deoxycholate (1 mg/kg on alternate days for 30 days; n = 51) liposomal <B>AmphotericinB> B (2 mg/kg per day for 5 days; n = 51) or <B>AmphotericinB> B lipid complex (2 mg/kg per day for 5 days; n = 51). Infusion-associated reactions were frequent and persistent in suBjects treated with <B>AmphotericinB> B Deoxycholate. The illness of 3 patients failed to respond to treatment and 5 patients experienced relapse. Final cure rates were similar. Estimated total treatment costs for a 25-kg patient -$417 for <B>AmphotericinB> B Deoxycholate$872 for liposomal <B>AmphotericinB> B and$947 for <B>AmphotericinB> B lipid complex - differed as a result of drug cost. SuBstantial reductions (~60%) in the price of liposomal <B>AmphotericinB> B and <B>AmphotericinB> B lipid complex would make treatment costs comparaBle to that of <B>AmphotericinB> B Deoxycholate permitting administration of short-course regimens in India. (authors)
Katrin Furrer - One of the best experts on this subject based on the ideXlab platform.
-
Nephrotoxicity of cyclosporine A and <B>AmphotericinB> B-Deoxycholate as continuous infusion in allogenic stem cell transplantation.
Swiss medical weekly, 2002Co-Authors: Katrin Furrer, Alexander Imhof, Andreas Schaffner, Stephan R Vavricka, Joerg Halter, Urs SchanzAbstract:Nephrotoxicity is an important side effect of amphothericin B Deoxycholate (ampho B) and cyclosporine A (CsA). The comBined administration of these drugs is frequent in patients with haematological diseases undergoing allogeneic stem cell transplantation. To assess the additional renal toxicity of ampho B given as a continuous infusion in addition to CsA. In a retrospective study renal function was investigated in patients receiving CsA alone or in comBination with ampho B (24-hour infusion) after allogeneic stem cell transplantation Between January 1998 and April 2001. Of a total of 84 patients, 22 were treated with ampho B. There was a statistically significant decline in renal function in comparison to the 62 patients receiving CsA alone. However, renal insufficiency in all patients remained in a clinically acceptaBle range and was reversiBle. The residual renal dysfunction at the end of the hospitalisation was mainly due to continuing therapy with CsA. <B>AmphotericinB> B Deoxycholate in addition to CsA leads to a statistically significant But clinically toleraBle worsening of renal function. Using a 24-hour infusion and strict salt repletion, <B>AmphotericinB> B can Be administered safely as Deoxycholate in Bone marrow transplant patients in conjunction with CsA for proven or suspected fungal infections.
-
Nephrotoxicity of cyclosporine A and <B>AmphotericinB> B-Deoxycholate as continuous infusion in allogenic stem cell transplantation.
Swiss Medical Weekly, 2002Co-Authors: Katrin Furrer, Alexander Imhof, Andreas Schaffner, Vavricka, Jörg Halter, Urs SchanzAbstract:Background Nephrotoxicity is an important side effect of amphothericin B Deoxycholate (ampho B) and cyclosporine A (CsA). The comBined administration of these drugs is frequent in patients with haematological diseases undergoing allogeneic stem cell transplantation. Aim To assess the additional renal toxicity of ampho B given as a continuous infusion in addition to CsA. Methods In a retrospective study renal function was investigated in patients receiving CsA alone or in comBination with ampho B (24-hour infusion) after allogeneic stem cell transplantation Between January 1998 and April 2001. Results Of a total of 84 patients, 22 were treated with ampho B. There was a statistically significant decline in renal function in comparison to the 62 patients receiving CsA alone. However, renal insufficiency in all patients remained in a clinically acceptaBle range and was reversiBle. The residual renal dysfunction at the end of the hospitalisation was mainly due to continuing therapy with CsA. Conclusion <B>AmphotericinB> B Deoxycholate in addition to CsA leads to a statistically significant But clinically toleraBle worsening of renal function. Using a 24-hour infusion and strict salt repletion, <B>AmphotericinB> B can Be administered safely as Deoxycholate in Bone marrow transplant patients in conjunction with CsA for proven or suspected fungal infections.