Evaluation of the echinocandin antifungal MK-0991 (L-743,872): efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis

• DOI: 10.1128/aac.41.11.2333
• Publication Date: 2018-10-09T00:27:12Z
• Authors: G K Abruzzo; A M Flattery; C J Gill; L Kong; J G Smith; V B Pikounis; J M Balkovec; A F Bouffard; J F Dropinski; H Rosen; H Kropp; K Bartizal
• Keywords: Candida parapsilosis; Candida krusei; Echinocandins; Candida glabrata; Systemic candidiasis

The in vivo activity of the Merck antifungal echinocandin drug candidate MK-0991 (L-743,872) was evaluated mouse models disseminated candidiasis, aspergillosis, and cryptococcosis. echinocandins are potent inhibitors 1,3-beta-D-glucan synthase. Two candidiasis were used. In a Candida albicans survival model with both DBA/2N CD-1 mice, estimates 50% effective doses (ED50s) 0.04 0.10 mg/kg body weight/dose at 21 days after challenge, respectively. C. target organ assay (TOA) levels > or =0.09 mg/kg/dose significantly reduced numbers CFU/g kidneys compared to control mice from 1 28 challenge. Even when given as single intraperitoneal dose either 30 min 24 h kidney those controls. >300-fold less active it administered orally than parenterally. efficacious TOAs against other strains species including tropicalis, (Torulopsis) glabrata, lusitaniae, parapsilosis, krusei. ineffective Cryptococcus neoformans infections. aspergillosis =0.02 prolonged ED50 ED90 being 0.03 0.12 mg/kg/dose, respectively, is potent, parenterally therapeutic agent that warrants further investigation human clinical trials.