Amphotericin animal studies

The interaction of amphotericin with serum lipoproteins (6) suggests that manipulations of blood lipids and blood lipoproteins might affect the pharmacokinetics of amphotericin, and therefore also alter its activity, including toxic effects, as suggested in animal studies (17). 

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). 

In vitro studies and experiments in animals have given conflicting results relating to potential antagonism between the effects of fluconazole and amphotericin on Candida species (149). However, large, randomized, doubleblind comparisons of fluconazole with and without amphotericin for 5 days in non-neutropenic patients with candidemia showed no evidence of antagonism, but faster clearance of the organism from the blood and a trend toward an improved outcome in those who received the combination (151). 

Mayer J, Doubeck M, Doubeck J, et al. Reduced nephrotoxicity of conventional amphotericin B therapy after minimal nephro-protective measures animal experiments and clinical study. J Am Soc Nephrol 2002. 

Methods - A standardized procedure for vitro susceptibility testing with 5-fluorocytoslne (Ancobon) which permitted both more accurate and more reproducible results was described.5 Two new experimental in vivo models were reported one dealt with cladosporiosls in mice treated with 5-fluoro-cytosine and the second with experimental urinary tract infections in rats caused by Candida albicans. In the former model, 5-fluorocytosine protected experimentally Infected animals against cerebral disease caused by Cladosporium tricholdes but did not clear the tissues of infection in the latter model, infections due to . albicans were treated successfully with amphotericin B, and the model appears useful in the study of anticandldal agents. 

Preliminary data were reported on the successful use of combinations of amphotericin B and 5-fluorocytosine in treatment of human cryptococcosis. 37 This mode of therapy, based on the earlier demonstration of a synergistic action between the two drugs vitro against yeasts,33 was validated experimentally in animals. In one study in mice infected with Candida albicans, CD50 dosages of amphotericin B were reduced in the presence of an otherwise inactive dose of 5-fluorocytosine.39 An additive effect for the two drugs was observed in mice infected with Cryptococcus neoformans. 0... 

---