Efficacy of alternative dosing regimens of poly-aggregated amphotericin B.
A new poly-aggregated form of amphotericin B was formulated as a non-microencapsulated form (P-AMB) or incorporated in albumin microspheres (MP-AMB) and compared with the conventional amphotericin B formulation (D-AMB). Mice were infected with Candida albicans and treated with two different intermittent dose regimens of the different amphotericin B formulations. Efficacy and toxicity were studied by the determination of survival rate, kidney colony-forming units counts, biochemical parameters and amphotericin B concentrations in plasma and organs. All the treatments significantly (P<0.05) increased the survival rate in relation to the untreated group, although non-statistically significant differences (P>0.05) were found between formulations and dosing regimens. All the treatments produced kidney toxicity, expressed by high urea levels. Kidney toxicity was especially significant for mice treated with the D-AMB formulation where unilateral kidney atrophy was observed in most of the mice, whereas most of the mice treated with P-AMB conserved both kidneys with a normal size and appearance. At 45 days post infection, variable distribution of amphotericin B in the body was obtained depending on the amphotericin B formulation. In conclusion, non-daily dosing regimens of P-AMB, which is less toxic than D-AMB, could be used as an alternative to the conventional D-AMB formulation to treat experimental candidiasis.
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid, Spain.
Raquel
R
Espada
Suriñe
S
Valdespina
Gloria
G
Molero
María A
MA
Dea
María P
MP
Ballesteros
Juan J
JJ
Torrado
D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D000825:Animal Structures / Q000737:chemistry; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D001284:Atrophy / Q000139:chemically induced; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical; D005260:Female; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D010949:Plasma / Q000737:chemistry; D016019:Survival Analysis
D000935:Antifungal Agents; D000666:Amphotericin B