Administration of Lipid-Emulsion Versus Conventional Amphotericin B in Patients with Neutropenia

Abstract

The clinical tolerance of lipid-emulsion infusions is similar to that of conventionally administered amphotericin B therapy. Renal toxicity appears to be decreased when the drug is administered in a fat emulsion. This type of preparation permits the reduction of the volume and the time of administration for amphotericin B therapy.

Decrease in Fungizone™ Toxicity Induced by the Use of Lipofundin™ As a Dilutent: An In Vitro Study

“…Systemic fungal infections induced by opportunistic microorganisms remain the major problem during the hospitalization of neutropenic patients, who have cancer or immune-compromised diseases [1][2][3]. The great availability of broad-spectrum antibacterial agents has increased the frequency and severity of fungal infections [1].…”

“…Although new antifungal agents have recently became available, amphotericin B (AmB) remains the drug of choice for the majority of systemic fungal infections in immunocompromised patients [1,[4][5][6][7][8][9][10][11][12]. Also, AmB has been frequently used as empiric therapy in granulocytopenic *Address correspondence to this author at the Departamento de Farmácia, Rua Praia de Areia Branca, 8948, Natal-RN, 59094-450, Brazil; Tel: 55-84-9431-8816; Fax: 55-84-215-4355; E-mail: socrates@digi.com.br or socrates@ufrnet.br patients with fever of unknown origin [1,5,13,14]. This molecule is able to interact with membrane sterols, cholesterol of the human plasmatic membranes and ergosterol of the fungal cell membranes, and form channels, which allow the leakage of the internal constituents, such as potassium, calcium, magnesium and phosphate.…”

“…However, the clinical use of Fungizone™ is frequently limited by the high incidence of adverse reactions, mainly, fever chills and nephrotoxicity, [1,[25][26][27][28][29]. A normal approach consists of the incorporation of AmB into lipidic structures, such as liposomes [3][4][5]18,[30][31][32], emulsions [1,10,27,[33][34][35][36], and colloidal complexes of AmB and cholesterol sulfate [6,37]. A normal approach consists of the incorporation of AmB into lipidic structures, such as liposomes [3][4][5]18,[30][31][32], emulsions [1,10,27,[33][34][35][36], and colloidal complexes of AmB and cholesterol sulfate [6,37].…”

“…Efforts have been made to develop less toxic formulations of AmB. In spite of the benefits induced by such formulations, several studies demonstrate that the largest disadvantage of these new formulations is their high cost when compared to the conventional Fungizone™ formulation [1,10,27,36,38]. In spite of the benefits induced by such formulations, several studies demonstrate that the largest disadvantage of these new formulations is their high cost when compared to the conventional Fungizone™ formulation [1,10,27,36,38].…”

“…While some groups adopt the procedure of simply dissolving Fungizone™ with Intralipid™ or Lipofundin ™ [33,47,48], others prefer to dissolve first the Fungizone™ with water for injectable preparations, as suggested by the manufacturer, and then dilute the Intralipid™ of Lipofundin™ with this preparation [1]. While some groups adopt the procedure of simply dissolving Fungizone™ with Intralipid™ or Lipofundin ™ [33,47,48], others prefer to dissolve first the Fungizone™ with water for injectable preparations, as suggested by the manufacturer, and then dilute the Intralipid™ of Lipofundin™ with this preparation [1].…”