Comparative pharmacokinetics of amphotericin B after administration of a novel colloidal delivery system, ABCD, and a conventional formulation to rats

Fielding, Robert M.; Smith, Philip C.; Wang, L. H.; Porter, James A.; Guo, Lin

doi:10.1128/aac.35.6.1208

Cited by 113 publications

(55 citation statements)

References 19 publications

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“…ABCD manteve sua ação antifúngica no tratamento de aspergilose em coelhos (Patterson et al, 1989) e sua administração em camundongos com candidíase levou à redução do número de unidades formadoras de colônia (UFC) nos rins, sugerindo ação do antifúngico mesmo com as baixas concentrações atingidas nesse órgão (Fielding et al, 1991).…”

Section: Estudos Em Animaisunclassified

“…Entretanto, os resultados de estudo realizados com animais relataram diferenças entre ambas formulações. Segundo Fielding et al (1991), após dose única de ABCD (1,0 e 5,0 mg/kg) ou de AB-DOC (1,0 mg/kg) em ratos, os valores séricos de ABCD foram inferiores. Concentrações diminuídas foram encontradas em baço e pulmões, sendo observada redução de 3 a 7 vezes na concentração de ABCD nos rins, mas no fígado os valores de ABCD foram 2 a 3 vezes maiores e cerca de 100% da AB administrada nessa formulação foram recuperados no fígado 30 minutos após a injeção.…”

Section: Farmacocinética E Distribuição Tecidual Das Formulações Lipíunclassified

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Eficiência terapêutica das formulações lipídicas de anfotericina B

Filippin

Souza

2006

Rev. Bras. Cienc. Farm.

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Section: Estudos Em Animaisunclassified

Section: Farmacocinética E Distribuição Tecidual Das Formulações Lipíunclassified

Eficiência terapêutica das formulações lipídicas de anfotericina B

Filippin

Souza

2006

Rev. Bras. Cienc. Farm.

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“…Colloidal systems have been successfully used for changing tissue distribution pattern of drug and selective targeting to the brain (10). Polymeric nanoparticles (NPs) can entrap the drug and act as drug reservoirs with sustained release and reduce the systemic exposure to free drug and toxicity associated with the same (11,12).…”

Section: Introductionmentioning

confidence: 99%

Protein-Functionalized PLGA Nanoparticles of Lamotrigine for Neuropathic Pain Management

et al. 2014

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Abstract. Lamotrigine (LTG), a sodium and calcium channel blocker, has demonstrated efficacy for the treatment of neuropathic pain in multiple, randomized, controlled trials. However, its potential clinical applications in neuropathic pain are limited due to the risk of dose-dependent severe rashes associated with high dose and prompt dose escalation. Further, the poor pharmacokinetic profile due to non-selective distribution to organs other than brain reduces the efficacy of dosage regimen. Therefore, the aim of present investigation is to develop surface-engineered LTG nanoparticles (NPs) using transferrin and lactoferrin as ligand to deliver higher amount of drug to brain and improve the biodistribution and pharmacokinetic profile of drug with prolonged duration of action and reduced accumulation in nontarget organs. The LTG NPs were prepared by nanoprecipitation and optimized by factorial design for high entrapment and optimized particle size. The optimized NPs were surface functionalized by conjugating with the lactoferrin (Lf) and transferrin (Tf) as ligands. The developed NPs were characterized for different physicochemical parameters and stability. The in vivo biodistribution showed preferential targeting to brain and reduced accumulation in non-target organs over a prolonged duration of time. Finally, partial sciatic nerve injury model was used to demonstrate the increased pharmacodynamic response as antinociceptive effect. Both biodistribution and pharmacodynamic study in mice confirmed that the approach used for LTG can help to increase clinical applications of LTG due to brain targeting and reduced side effects.

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“…[10][11][12][13] ABCD has been shown to be significantly less toxic than conventional amphotericin B in animals, without reduction in efficacy, permitting administration of higher doses. 14,15 In experimental infections, laboratory animals responded to ABCD and conventional amphotericin B at similar rates, but safety was demonstrated at ABCD doses that were five to eight times higher than doses of conventional amphotericin B. 16 In clinical trials, ABCD has been shown to be safe and well tolerated.…”

mentioning

confidence: 99%

Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients

Noskin

Pietrelli

Gurwith

et al. 1999

Bone Marrow Transplant

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Summary:Amphotericin B colloidal dispersion (ABCD, AMPHO-TEC, AMPHOCIL), a lipid complex of amphotericin B, was developed to reduce the nephrotoxicity of amphotericin B while retaining its antifungal efficacy. In this retrospective review, the efficacy and safety of ABCD were evaluated in 220 BMT recipients (167 allogeneic; 53 autologous) with suspected or documented lifethreatening fungal infections (primarily Candida or Aspergillus species). Patients were treated in five openlabel clinical trials of ABCD therapy. ABCD was administered intravenously once daily, median dose of 4 mg/kg, for up to 409 days (mean 23 days, median 16 days). Successful therapeutic response to treatment (complete or partial) was reported in 52% of the 99 evaluable patients with proven infection, and in 40% of all 220 patients. In the evaluable population, the response and mortality rates were 51% and 73%, respectively, in the allogeneic BMT patients, compared to 52% and 48% in the autologous BMT patients. The response rate for evaluable patients with Candida spp was 65%, 38% for patients with Aspergillus spp, and 42% for patients with other or multiple fungal infections. In this patient population at high risk of nephrotoxicity due to concomitant cyclosporine and/or other nephrotoxic agents, ABCD did not cause renal dysfunction. Although the majority of patients had pre-existing renal impairment (median baseline serum creatinine 1.8 mg/dl), there was no trend towards increasing serum creatinine. No unexpected toxicities were observed. In conclusion, ABCD appears to be safe and effective for the treatment of severe fungal infections in BMT patients. Keywords: ABCD; amphotericin B cholesteryl sulfate for injection; amphotericin B colloidal dispersion; marrow transplant; fungal infection; nephrotoxicity Opportunistic fungal infections are an increasing cause of morbidity and mortality in bone marrow transplant (BMT) patients. evolved, the problem of invasive fungal infection has assumed increased significance. In reports from marrow transplant centers 1-3 the incidence of systemic fungal infections ranges from 4 to 30% with a mortality rate approaching 100%. 4 The administration of prophylactic fluconazole may decrease the incidence of documented systemic fungal infection following high-dose chemotherapy and BMT. 5,6 However, despite fluconazole prophylaxis, over half of patients still require empiric therapy with amphotericin B for prolonged unexplained febrile episodes. 5 Additionally, fluconazole is not effective against Aspergillus spp infections and certain species of Candida, such as C. krusei and most strains of C. glabrata.Amphotericin B, a polyene antibiotic that has been used to treat fungal infections for four decades, is still considered the most reliable agent for therapy of mycoses in immunosuppressed patients. However, its well known adverse effects, particularly dose-limiting nephrotoxicity, often complicate and limit its effective use. 7 Although the reported incidence is quite variable, two recent reviews estimate that 6...

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Comparative pharmacokinetics of amphotericin B after administration of a novel colloidal delivery system, ABCD, and a conventional formulation to rats

Cited by 113 publications

References 19 publications

Eficiência terapêutica das formulações lipídicas de anfotericina B

Eficiência terapêutica das formulações lipídicas de anfotericina B

Protein-Functionalized PLGA Nanoparticles of Lamotrigine for Neuropathic Pain Management

Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients

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