Efficacy of the investigational echinocandin ASP9726 in a guinea pig model of invasive pulmonary aspergillosis

Antimicrobial Agents and Chemotherapy
Nathan P WiederholdThomas F Patterson

Abstract

ASP9726 is an investigational echinocandin with in vitro activity against Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with A. fumigatus AF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1 → 3)-β-D-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1 → 3)-β-D-glucan and galactomannan levels, but only voriconazole significantly ...Continue Reading

References

Feb 28, 1996·JAMA : the Journal of the American Medical Association·P A NuttingS Holcomb
Feb 15, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·S J LinS M Teutsch
Aug 17, 2002·Antimicrobial Agents and Chemotherapy·J C BowmanC M Douglas
Dec 20, 2002·The New England Journal of Medicine·Jorge Mora-DuarteUNKNOWN Caspofungin Invasive Candidiasis Study Group
Jul 29, 2003·Expert Opinion on Investigational Drugs·Nathan P Wiederhold, Russell E Lewis
Sep 25, 2003·Blood·Kieren A MarrGeorge B McDonald
Apr 24, 2004·Antimicrobial Agents and Chemotherapy·Donald C SheppardAshraf S Ibrahim
Jul 2, 2004·American Journal of Respiratory and Critical Care Medicine·Wouter MeerssemanEric Van Wijngaerden
Oct 9, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Kieren A MarrLawrence Corey
Dec 4, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Johan MaertensUNKNOWN Caspofungin Salvage Aspergillosis Study Group
Jul 1, 2005·Critical Care : the Official Journal of the Critical Care Forum·José Garnacho-MonteroFernando Barcenilla
Sep 29, 2006·Antimicrobial Agents and Chemotherapy·Donald C SheppardScott G Filler
May 8, 2007·Lancet·Ernst-Rüdiger KuseUNKNOWN Micafungin Invasive Candidiasis Working Group
Jun 15, 2007·The New England Journal of Medicine·Annette C ReboliUNKNOWN Anidulafungin Study Group
Sep 7, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Peter G PappasDonald N Buell
Nov 3, 2007·Current Opinion in Infectious Diseases·Nathan P Wiederhold
Nov 6, 2008·Transplant Infectious Disease : an Official Journal of the Transplantation Society·D P KontoyiannisK A Marr
Mar 4, 2009·Medical Mycology·Nathan P Wiederhold
Mar 6, 2009·Journal of Clinical Microbiology·M L HerreraB L Wickes
Jan 29, 2014·Bioorganic & Medicinal Chemistry Letters·Hiroshi MorikawaKatsuyuki Maki

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Citations

Sep 17, 2015·Current Opinion in Infectious Diseases·Nathan P Wiederhold, Thomas F Patterson
Oct 22, 2016·MedChemComm·Huy X NgoKeith D Green
Nov 26, 2016·Biochemical Pharmacology·Sonia Campoy, José L Adrio
Aug 14, 2019·Antimicrobial Agents and Chemotherapy·Nathan P WiederholdThomas F Patterson
Jul 17, 2020·Frontiers in Cellular and Infection Microbiology·Chukwuemeka Samson AhamefuleWenxia Fang
Jun 1, 2017·Frontiers in Microbiology·Guillaume Desoubeaux, Carolyn Cray
Nov 5, 2019·Frontiers in Microbiology·Karen G N OshiroOctávio Luiz Franco
Jul 22, 2020·Journal of Medicinal Chemistry·Wei LiuShengzheng Wang
Nov 20, 2021·International Journal of Antimicrobial Agents·Chibuike IbeOmran Alamir

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