AmBisome

Liposomal amphotericin B (AmBisome) may be more appropriate for disseminated disease. 

Lipid-associated formulations of amphotericin B, liposomal amphotericin B (AmBisome) and amphotericin B lipid complex (Abelcet) have been approved for use in proven cases of candidiasis however, patients with invasive candidiasis have also been treated successfully with amphotericin B colloid dispersion (Amphotec or Amphocil). The lipid-associated formulations are less toxic but as effective as amphotericin B deoxycholate. 

Solid-organ transplantation Liver transplantation Micafungin 50 mg (1 mg/kg in patients under 50 kg) IV daily Patients with two or more key risk factor Amphotericin B IV 10-20 mg daily or Liposomal amphotericin B (AmBisome) 1 mg/kg/day or flucona-... 

The three commercially available AmB formulations differ in their morphology, their composition, and, consequently, their biological activity. AmBisome (developed by Nexstar Pharmaceuticals, commercially available from Gilead Sciences) is a true liposome formulation, consisting of small, unilamellar vesicles (9). Their small size confers a prolonged circulation time... 

For the purposes of comparison, commercial AmB-lipid formulations were obtained as follows. Amphotec was obtained from Intermune (U.S.A.). AmBisome and Abelcet were kind gifts from Gilead Sciences (Foster City, California, U.S.A.) and Zedeus Pharma (Versailles, France), respectively. Ampholiposomes (cationic oligolameller liposomes containing AmB) were supplied by the Pharmacie Centrale des Hopitaux (Paris, France). 

Table 2 shows the results obtained for four-hour and 24-hour exposure to AmB. LC-AmB had an IC50 above lOOmg/L after 24-hour exposure. This indicates that it has very low toxicity, comparable to the commercial formulation AmBisome (9). The toxicity increased with the time of exposure for all formulations (after a 48-hour exposure, the IC50 of LC-AmB was 86mg/L, data not shown). Very similar results were obtained in the presence of polymyxin B, eliminating the possibility that the toxicity was due to the contamination of the formulations with lipopolysaccharide (LPS) (22). 

In one experiment, LC-AmB was compared with AmBisome (small unilamellar liposomes). LC-AmB was found to have an ED50 of 0.19 mg/kg and an ED90 of 0.51 mg/kg, whereas for AmBisome both these parameters were below 0.20 mg/kg, the lowest dose tested. In another experiment, LC-AmB was compared with Abelcet and showed a better reduction of parasite burden after three injections of 1 mg/kg, but there were not sufficient data to allow ED50 values to be calculated (22). Therefore, we can conclude that this new AmB formulation retains antileishmanial activity in vivo, but it is difficult to position it with respect to other formulations. 

This technique allowed us to prepare small colloids with a high proportion of AmB (33% molar proportion compared with 5% in AmBisome). However, at present we have used expensive, synthetic phospholipids. It may be possible to replace DMPC and DMPG by natural or partially hydrogenated natural phospholipids such as those from egg yolk or soy. This sort of economic consideration must be taken into account for the future development of the formulation. 

Alder-Moore JP, Proffitt R. Development, characterisation, efficacy and mode of action of AmBisome, a unilamellar liposomal formulation. J Liposome Res... 

Cryptococcal meningitis in HIV Treatment of cryptococcal meningitis in HIV-infected patients AmBisome only). 

Liposomai amphotericin B (AmBisome) - The recommended dose is 3 to 5 mg/kg/day prepared as a 1 to 2 mg/mL infusion delivered initially over 120 minutes infusion time may be reduced to 60 minutes if well tolerated or increased if patient experiences discomfort. Lower infusion concentrations of... 

Liposomal amphotericin B (AmBisome) - Administer 3 mg/kg/day on days 1 through 5, 14 and 21 to immunocompetent patients a repeat course of therapy may be useful if parasitic clearance is not achieved. Administer 4 mg/kg/day on days 1 through 5, 10, 17, 24, 31, and 38 to immunosuppressed patients seek expert advice regarding further therapy if parasitic clearance is not achieved. 

Amphotericin B (Amphocin) Amphotericin B Cholesteryl (Amphotec) Amphotericin B Lipid Complex (Abelcet) Amphotericin B Liposomal (AmBisome) Anidulafungin (Eraxis)... 

Berman JD. Editorial response U. S. Food and Drug Administration approval of AmBisome (Liposomal Amphotericin B) for treatment of visceral leishmaniasis. Clin Infect Dis 1999 28 49-51. 

Brand Name(s) Abelcet (ABLC) AmBisome, Amphotec, Fungizone (IV and topical) Chemical Class Amphoteric polyene lipid complex (ABLC)... 

Pharmacokinetics Protein binding 90%. Widely distributed. Metabolic fate unknown. Cleared bynonrenal pathways. Minimal removal by hemodialysis. Amphotec and Abelcet are not dialyzable. Amphotec Half-life 26-28 hr. Abelcet Half-life 7.2 days. AmBisome Half-life 100-153 hr. 

Empiric treatment for fungal infection in patients with febrile neutropenia foraspergil-lus, Candida, or cryptococcus infections unresponsive to Fungizone or for patients with renalimpairmentortoxicityfromFungizone(AmBisome) IVInfusion 3-5 mg/kg over 1 hr. 

Abelcet-. Chills, fever, increased serum creatinine, multiple organ failure AmBisome-. Hypokalemia, hypomagnesemia, hyperglycemia, hypocalcemia, edema, abdominal pain, back pain, chills, chest pain, hypotension, diarrhea, nausea, vomiting, headache, fever, rigors, insomnia, dyspnea, epistaxis, increased liver/renal function test results... 

Chopra, R., AmBisome in the treatment of fungal infections the UK experience. J Antimicrob Chemother, 2002.49(Suppl 1) 43-7. 

Abelcet) 100 mg/20 mL suspension for injection (AmBisome) 50 mg powder for injection (Amphotec) 50, 100 mg powder for injection Topical 3% cream, lotion, ointment Butoconazole (Gynazole-1, Mycelex-3)... 

Neopharm LED doxorubicin Inex onco TCS vincristine Neopharm LEP paclitaxel Elan inyocet doxorubicin Gilead ambisome amphoteracin Gilead daunXome daunorubicin Alza doxil doxorubicin QLT visudyn verteporfin... 

Ambisome , Daunoxome , liposomal amphotericin B and daunorubicin citrate injection. Liposomal lurtotecan in phase I clinical trials. Gilead Sciences Inc., Foster City, CA. 

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