Antifungal Activity, Plasma Pharmacokinetics and Safety of Second-generation Echinocandin ASP9726 in Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits

Ref ID: 18677

Author:

V. Petraitis, MD – Senior Research Associate in Medicine1, R. Petraitiene, MD – Senior Research Associate in Medicine 1, K. A. Such, DVM – Postdoctoral Associate 2, P. W. Moradi, BS – Research Technician 1, G. E. Strauss, BS – Research Technician 1,

Author address:

1Weill Cornell Med. Coll. of Cornell Univ., New York, NY, 2The Rockefeller Univ., Weill Cornell Med. Coll., and Mem. Sloan-Kettering Cancer Ctr., New York, NY, 3Covance Res. Products, Denver, PA, 4Astellas Pharma Inc, Tukuba, Ibaraki, Japan.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: The second-generation echinocandin ASP9726 (ASP) in vitro demonstrated superior activity in comparison to first-generation echinocandins. We therefore, studied the safety, antifungal activity, and pharmacokinetics of ASP in comparison to that of caspofungin (CFG) against experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. Methods: Treatment groups consisted of ASP at 1.5 (ASP1.5), 3 (ASP3), 6 (ASP6), CFG at 1.5 (CFG 1.5), 3 (CFG 3), 6 (CFG 6) mg/kg/day, and untreated controls (UC). Results: Rabbits treated with ASP3 and ASP6 showed a significant reduction in organism-mediated pulmonary injury as measured by infarct scores in comparison to that of CFG3, CFG6, and UC (p<0.05). ASP6-treated rabbits demonstrated mean lower lung weights in comparison to CFG6 and UC (p<0.05). There was significant reduction of residual fungal burden (CFU/g) in ASP6 treated rabbits in comparison to UC (p<0.05). By comparison, there were no significant decreases in infarct score, lung weights, and log CFU/g in CFG-treated rabbits in comparison to UC. There was significantly prolonged survival in ASP and CFG-treated rabbits in comparison of that to UC (p<0.01 and p<0.05, respectively). Conclusions: ASP9726 is a novel echinocandin, which decreases pulmonary injury, reduces residual fungal burden, and increases survival in experimental invasive pulmonary aspergillosis.

Abstract Number: M-981

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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