Experience with liposomal amphotericin B (AmBisome) in cryptococcal meningitis in AIDS

Coker, Richard; Murphy, SM; Harris, J. R. W.

doi:10.1093/jac/28.suppl_b.105

Cited by 18 publications

(5 citation statements)

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“…Estudos pré-clínicos e clínicos (fase I e II) indicaram que L-AmB foi bem tolerada e apresenta nefrotoxicidade reduzida em comparação à d-AmB [28][29][30][31] . Outras condições clínicas foram avaliadas, nos estudos iniciais com esta formulação, com eficácia comparável à d-AmB [32][33][34][35][36] . A L-AmB despontou como uma alternativa com um índice terapêutico muito mais favorável do que d-AmB, o que a tornou particularmente promissora para o tratamento de condições graves, como a aspergilose invasiva, histoplasmose disseminada e também a leishmaniose visceral, em que concentrações maiores de anfotericina B são necessárias para o controle infeccioso [37][38][39][40] 18 .…”

Section: Anfotericina B Lipossomalunclassified

Anfotericina B: uma revisão sobre suas diferentes formulaões, efeitos adversos e toxicidade

Falci¹,

Pasqualotto²

2015

cbr

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A incidência de infecções fúngicas invasivas tem aumentado, como consequência do contingente cada vez maior de pacientes com imunossupressão. O tratamento de infecções fúngicas com anfotericina B (AmB) está associado a efeitos adversos importantes, como nefrotoxicidade e toxicidade hematológica. Nesta revisão buscou-se abordar os estudos sobre AmB nas diferentes formulações, focando em suas características farmacológicas e toxicidade. Formulações lipídicas de AmB estão associadas a um risco menor de nefrotoxicidade, entretanto ainda há controvérsia sobre diferenças entre as duas formulações lipídicas de AmB disponíveis. Diferenças em relação ao perfil imunomodulatório e ligação a lipoproteínas podem explicar parte das diferenças clínicas existentes entre as formulações de AmB. A maioria dos estudos clínicos que avaliou a nefrotoxicidade associada à AmB em diferentes formulações não utilizou critérios validados para classificação do dano renal, o que dificulta sua comparação. A toxicidade hematológica relacionada ao uso de AmB é um fenômeno descrito desde os primórdios do seu uso clínico, entretanto poucos dados existem sobre sua frequência, fatores de risco e impacto nos desfechos clínicos. Dados precisos, e adequados ao contexto local, sobre a toxicidade de AmB nas suas diferentes formulações são necessários para uma adequada avaliação dos aspectos de farmacoeconomia e custo-efetividade.

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Section: Anfotericina B Lipossomalunclassified

Anfotericina B: uma revisão sobre suas diferentes formulaões, efeitos adversos e toxicidade

Falci¹,

Pasqualotto²

2015

cbr

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“…No difference between in vitro suscep tibility to conventional amphotericin B and that to the lipo somal drug has been found for the different fungal strains [101,102]. Open trials o f liposomal amphotericin B in neu tropenic patients and bone marrow recipients show-in com parison with the conventional drug-a similar or improved efficacy profile with a lower incidence o f side effects in the treatment o f infections due to Candida and Aspergillus spe cies [100,[103][104][105][106][107][108][109][110]; in contrast, descriptions o f isolated cases o f cryptococcal meningitis in patients with AIDS indi cate that the efficacy o f liposomal amphotericin B is not ideal [111]. Its safety profile in solid-organ transplantation and its expected efficacy in the treatm ent o f severe infections caused by Aspergillus, Candida, and Cryptococcus species remain to be evaluated.…”

Section: Treatmentmentioning

confidence: 99%

Fungal Infections in Solid-Organ Transplantation

Payá

1993

Clinical Infectious Diseases

353

209

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Fungal infections following solid-organ transplantation remain a major cause of morbidity and death. Their incidence ranges from 5% among recipients of kidney transplants to as high as 40% among recipients of liver transplants. Species of Candida and Aspergillus account for more than 80% of fungal episodes. Moreover, more than 80% of fungal infections occur within the first 2 months after transplantation, with a resulting mortality of 30%-100%. The pathogenesis of infection and the risk factors involved depend on the type of transplant and the infecting microorganism. Cyclosporine has not significantly reduced the incidence or severity of fungal infections in this population. The value of surveillance cultures and fungal antigen detection in solid-organ transplant recipients remains to be determined. Amphotericin B is still a first-line drug, but its potential nephrotoxicity makes its use problematic, especially in renal transplant recipients. Fluconazole is a potential alternative for the treatment of infections due to Candida species and Cryptococcus neoformans. The role of antifungal compounds in the prophylaxis of fungal infection in recipients of solid-organ transplants needs to be established.

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“…The small unilamellar vesicle liposomal amphotericin B (LAmB) formulation, known as AmBisome (Vestar, Inc., San Dimas, Calif.), differs from the others in that it forms true liposomes with uniform, stable, spherical, single-membraned vesicles of <0.1 ,um in diameter. Early clinical studies have suggested that LAmB is both safe and effective against cryptococcosis and candidiasis (3, 4,8,12).…”

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confidence: 99%

Pharmacokinetics and safety of a unilamellar liposomal formulation of amphotericin B (AmBisome) in rabbits

Lee

Amantea

Francis

et al. 1994

Antimicrob Agents Chemother

125

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A unilamellar liposomal formulation of amphotericin B (LAmB) known as AmBisome was safely administered intravenously to 20 rabbits at 0.5, 1.0, 2.5, 5, or 10 mg/kg of body weight, whereas of 12 rabbits given desoxycholate amphotericin B (DAmB) intravenously at 0.5, 1.0, or 1.5 mg/kg, 2 died of acute cardiac toxicity when DAmB was administered at the highest dose. Single-dose LAmB (1 mg/kg) achieved a maximum concentration in serum (Cmax) of 26 ± 2.4 ,ug/ml and an area under the curve to infinity (AUC O) of 60 ± 16 ,ug h/ml, while single-dose DAmB (1.0 mg/kg), by comparison, achieved a lower Cmax (4.7 ± 0.2 -ug/ml; P = 0.001) and a lower AUC -,, (30.6 ± 2.2 ,ug * h/ml; P = 0.07). Following administration of a single dose of LAmB (10 mg/kg), a disproportionately higher Cmax (287 ± 14 ,ug/ml) and AUC0_Q (2,223 ± 246 ,ug* h/ml) occurred, indicating saturable elimination. After chronic dosing (n = 4) with LAmB at 5.0 mg/kg/day for 28 days or DAmB at 1.0 mg/kg/day for 28 days, LAmB achieved daily peak levels of 122.8 ± 5.8 ,ug/ml and trough levels of 34.9 ± 1.8 ,ug/ml, while DAmB reached a peak of only 1.76 ± 0.11 ,ig/ml and a trough of 0.46 ± 0.04 ,ig/ml (P . 0.001). Significant accumulations of amphotericin B into reticuloendothelial organs were observed, with 239 ± 39 ,ug/g found in the liver after chronic LAmB dosing (5 mg/kg/day), which was seven times higher than the 33 ± 6 ,ug/g after DAmB dosing (1 mg/kg/day) (P = 0.002). Accumulation in kidneys, however, remained 14-fold lower (P = 0.04) following LAmB dosing (0.87 ± 0.61 j,g/g) than after DAmB dosing (12.7 + 4.6 ,ug/g). Nephrotoxicity occurred in only one of four LAmB-treated animals, while it occurred in all four chronically DAmB-treated animals; mild hepatotoxicity with transaminase elevations was seen in one MATERUILS AND METHODS Drugs. LAmB was provided as a lyophilized yellow powder (AmBisome) by Vestar, Inc. The drug's constituents are 53.3% hydrogenated soy phosphatidylcholine, 13.1% cholesterol, 21.1% distearoylphosphatidylglycerol, and 12.5% amphotericin B (by weight, or at a molar ratio of 2:1:0.8:0.4, respectively). The powder was initially reconstituted with sterile water to an initial concentration of 2 mg/ml, and the solution was then heated to 60°C for 10 min to ensure dissolution. The solution was then filtered through a 5-,um-pore-size filter to remove any aggregates that might remain and was diluted to a final concentration of 0.5 mg/ml with 5% glucose in water. DAmB was prepared from commercially available Fungizone (BristolMyers Squibb, Princeton, N.J.) by dissolving the initial powder with sterile water and then further diluting the solution with 5% glucose in water to a final concentration of 1 mg/ml.Rabbits. Female New Zealand White rabbits weighing between 2.5 and 3.0 kg were used for the study. Animals were housed individually and were provided food and water ad libitum. While the rabbits were under general anesthesia, a silastic central venous catheter was surgically placed in each rabbit for repeated, nontraumatic venous access as...

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Experience with liposomal amphotericin B (AmBisome) in cryptococcal meningitis in AIDS

Cited by 18 publications

References 0 publications

Anfotericina B: uma revisão sobre suas diferentes formulaões, efeitos adversos e toxicidade

Anfotericina B: uma revisão sobre suas diferentes formulaões, efeitos adversos e toxicidade

Fungal Infections in Solid-Organ Transplantation

Pharmacokinetics and safety of a unilamellar liposomal formulation of amphotericin B (AmBisome) in rabbits

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