Pharmacokinetic evaluation of liposomal amphotericin B in lung tumor patients

C Lequaglie, I Cataldo, B Conti, G Giudice, PP Brega Massone, G Demartini, F Fraschini, F Scaglione.

Abstract: 

Amphotericin B (AmB) is the choice drug in the treatment of the deep fungal diseases. It is useful in primitive and secondary deep infections (invasive or disseminated). The first limitation to treatment is the toxicity. L-AmB (AmBisome), like other formulations, made possible good results minimizing adverse reactions. Some mechanisms contribute to the reduced toxicity: the liposome-mediated transfer of AmB to fungal cell membranes; the reduced levels of AmB in the kidney in relation to the high levels achieved in the reticuloendothelial system; the selective local release of AmB directly onto the fungal cells. These characteristics explain the higher serum levels of L-AmB that persist in the flow more shorter than conventional AmB.Very few studies evaluated the lipid-formulations of AmB. The aim of this study was to verify the kinetic curves of L-AmB in the serum and in the lung tissue of lung cancer resected patients. We enrolled 20 adult (> 18 years) patients. L-AmB was administered by one hour infusion at fixed doses of 100 mg , and it was infused from 1 to 24 hours before the resection. The starting and the end points of infusion were noted, the same for arterial and vein ligature, and the point of pulmonary tissue sample collection. Moreover, 10 mi of blood sample at the artery closure were collected. AmB was assayed in blood and lung tissue by an HPLC validated method.The blood levels after 2 to 4 hours from the end of infusion (six patients) ranged from 10 to 40 mg/L, while the tissue levels ranged from 1,2 to 6,4 mglg; 8 to 12 hours after infusion blood levels (7 patients) ranged from 5,2 to 18 mg/I tissue levels in this period ranged from 6 to 15,8 mg/g; 20 to 24 hours after infusion blood levels and tissue levels ranged from 2,3 to 12,4 mg/I and 3.2 to 15,3 mg/g respectively. In conclusion, these data support the consistent lung tissue diffusion of L-AmB in patients with primary and secondary lung cancer. The value of the concentrations appears lower to similar the blood one. Lung concentrations of L-AmB fit with the lower Volume of Distribution of this formulation than AmB, reported from some authors.
2001

abstract No: 

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Full conference title: 

Trends in Invasive fungal Infections 6, 2001
    • TIFI 6th