Amphotericin L-AmB

ABLC = Amphotericin B Lipid Complex ABCD = Amphotericin B Colloidal Dispersion L-AMB = Liposomal Amphotericin B... 

Amphotericin B Abelcet (ABLC) [injectable 5 mg/ml, Upid complex],Ambisome (L-AMB) [injectable 50 mg/vial,liposomal].Amphocin (injectable 50 mg/vial, nonlipid),Amphotec (ABCD) [injectable 50 mg/vial, 100 mg/vial, colloidal dispersion], Fungizone [injectable 50 mg/vial, nonlipid], generic also available. 

Ocular penetration of IV amphotericin B is inflammation dependent and the liposomal formulation (L-AMB). May reach the highest aqueous and vitreous concentrations. 

Goldblum et al. studied the ocular penetration of IV amphotericin B and its lipid formulations in a rabbit model and determined L-AMB achieved at least eightfold higher amphotericin B concentrations in the aqueous of inflamed eyes when compared with ABLC or amphotericin B. 

Lipid formulations of amphotericin have individually variable pharmacokinetics. The use of DAMB in 20% Intralipid results in marked changes, with lower antifung-ally active blood concentrations (13). Infusion of ABLC, ABCD, or L-Amb, AmBisome results in plasma amphotericin concentrations specific to the individual formulation. The half-life of amphotericin after lipid formulations is prolonged compared with the deoxycholate formulation (14) 4-10 days for ABCD (15) and about 5 days for ABLC (16). The importance of these differences is unknown, because they do not reflect the biologically active concentration of amphotericin, which also varies with formulation. On a weight for weight basis amphotericin in lipid formulations is less active than in the deoxycholate formulation, because of lower systemic availability (5). One factor that complicates the interpretation of blood concentrations is the sparse data... 

Cholestasis has been reported in infants treated with amphotericin for systemic Candida infections (SEDA-14, 230). Most of the above reports were incidental, and amphotericin cannot be regarded as a known cause of liver damage. This does not necessarily also apply to liposomal amphotericin and other lipid formulations. Therapy with L-Amb, AmBisome was associated with a rise in alkaline phosphatase in over a third of children treated with AmBisome (93) and with hepatic dysfunction in a little under 20% of adolescents and adults. In a small retrospective study, ABLC was withdrawn in 27% of patients because of rises in serum bilirubin and alkaline phosphatase, a finding confirmed in a larger prospective study. Cholestasis has also been observed with ABCD, in contrast to reports that L-AmB does not increase transaminases (5). 

In a prospective double-blind study of more than 600 patients, 0.6 mg/kg of DAMB was compared with 3.0 mg/kg of L-Amb, a dose relation at the lower limit of equivalent doses determined in an animal model (117). At these dosages, in a large prospective double-blind study, there was a doubling of serum creatinine concentration in 19% of neutropenic patients receiving empirical therapy with L-AmB and 34% receiving conventional amphotericin (47). 

Sable CA, Villanueva A, Arathon E, Gotuzzo E, Turcato G, Uip D, Noriega L, Rivera C, Rojas E, Taylor V, Berman R, Calandra GB, Chodakewitz J. A randomized, double-blind, multicenter trial of MK-991 (L-743,872) vs. amphotericin B (AMB) in the treatment of Candida esophagitis in admts. Abstracts of the 37th Interscience Comerence on Antimicrobial Agents and Chemotherapy, 1997 LB-33. 

In a systematic review of the risk of nephrotojddty induced by two different lipid formulations of amphotericin, amphotericin B lipid complex (ABLC) and liposomal amphotericin B (l-AtuB), 11 studies were identified and 8 were included [5 ]. There was a higher probability of nephrotoxicity in patients who received ABLC versus L-AmB (OR=1.75 RR = 1.55), but there was a significant lack of homogeneity across these studies. Restricted analyses, omitting different studies that contributed to the heterogeneity, showed that the risks were more similar between the two formulations. 

Electrolyte balance Of 25 Japanese subjects with fungal infections treated with L-AmB, one had a raised serum creatinine and six had hypokalemia-, there was a positive relation between the fall in serum potassium and the dose of amphotericin, and the serum potassium tended to fall after 5-6 days [9 ]. 

Observational studies A prospective study investigated the effectiveness and safety of liposomal amphotericin B (L-AmB) therapy in critically ill paediatric patients Altogether, 23 critically ill patients were included (nine females, mean age 26.4 months, range, 5-39 months) and they received L-AmB for a median of 10 days (range, 3-28 days). Two cases of hepatotoxicity and one case of nephrotoxicity leading to discontinuation of therapy were recorded. Seven cases of mild reversible hypokalaemia and five cases of hyponatremia were also reported. 

Transient azotemia occurs in 80% of patients who receive C-AMB for deep mycoses. Toxicity is dose-dependent and increased by concurrent therapy with other nephrotoxic agents (e.g., aminoglycosides, cyclosporine). Permanent impairment is uncommon in adults with normal renal function unless the cumulative dose is >3-4 g. Renal tubular acidosis and wasting of K and Mg also may occur during and for several weeks after therapy, often requiring repletiort Administration of 1 L of normal saline intravenously prior to C-AMB administration is recommended for adults who can tolerate the Na load. Azotemia occurs less frequently with lipid preparations of amphotericin, and saline loading is not needed. 

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