title: Efficacy and toxicity of a tropically stable lipid-based formulation of amphotericin B (iCo-010) in a rat model of invasive candidiasis.
abstract: The objective of this work was to assess the antifungal activity of a tropically stable formulation of amphotericin B (AmB) (iCo-010) over short period of treatment in a rat model of invasive candidiasis. The rats were infected with Candida albicans (ATCC 18804); 48 h later, the animals were assigned either to a control group, AmBisome(®) group (5 mg/kg QD), or iCo-010 groups (0.5, 1, 2.5, 5 and 10 mg/kg TID). The animals were treated for two days and then sacrificed 18 h following the completion of the treatment. The blood, liver, lungs, kidneys and spleen were harvested to assess the colony forming units in the samples. There was no significant difference in the reduction of the fungal burden in the organs between the AmBisome(®) and iCo-010 groups except in the spleen and liver. There was a linear correlation between the antifungal activity in renal tissues and the administered doses of iCo-010. The plasma creatinine levels were not significantly different among the control and all the treatment groups. Oral iCo-010 has high efficacy against invasive candidiasis in renal and pulmonary tissues. Longer treatment period than the two-days regimen should be considered for higher therapeutic efficacy of iCo-010 in all the tissues.
authors: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors: Fady
authors: F
authors: Ibrahim
authors: Pavel
authors: P
authors: Gershkovich
authors: Olena
authors: O
authors: Sivak
authors: Ellen K
authors: EK
authors: Wasan
authors: Karen
authors: K
authors: Bartlett
authors: Kishor M
authors: KM
authors: Wasan
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D058365:Candidiasis, Invasive / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000382:microbiology; D008055:Lipids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000382:microbiology
chemical_list: D000935:Antifungal Agents; D008055:Lipids; D000666:Amphotericin B; D003404:Creatinine