Efficacy of ravuconazole (BMS-207147) in a guinea pig model of disseminated aspergillosis

• Published in: Journal of antimicrobial chemotherapy Vol. 49; no. 2; pp. 353 - 357
• Main Authors: Kirkpatrick, William R., Perea, Sofia, Coco, Brent J., Patterson, Thomas F.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2002; Oxford Publishing Limited (England)
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Aspergillosis - drug therapy; Aspergillosis - microbiology; Aspergillosis - mortality; Aspergillus fumigatus - drug effects; Aspergillus fumigatus - isolation & purification; Biological and medical sciences; Disease Models, Animal; Drug Evaluation, Preclinical - methods; Drug Evaluation, Preclinical - statistics & numerical data; Guinea Pigs; Humans; Male; Medical sciences; Organ Culture Techniques; Organ Specificity - drug effects; Pharmacology. Drug treatments; Thiazoles - pharmacology; Thiazoles - therapeutic use; Triazoles - pharmacology; Triazoles - therapeutic use; Opportunistic infection; Leukopenia; Mycosis; Rodentia; Ravuconazole; Oral administration; Hemopathy; Long term; Fungi; Infection; Vertebrata; Antifungal agent; Chemotherapy; Immunosuppression; Mammalia; Guinea pig; Treatment; Animal; Aspergillosis; Complication; Fungi Imperfecti; Aspergillus fumigatus; Thallophyta; Neutropenia
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/49.2.353

Ravuconazole (BMS-207147, ER-30346), an oral triazole, was evaluated in an immunosuppressed temporarily neutropenic guinea pig model of invasive aspergillosis. In this model, guinea pigs were immunosuppressed with triamcinolone 20 mg/kg sc od beginning 4 days before challenge and made neutropenic with cyclophosphamide 300 mg/kg ip 1 day before challenge. Treatments of ravuconazole 5, 10 and 25 mg/kg po od were compared with itraconazole 2.5 and 5.0 mg/kg po bd and amphotericin B 1.25 mg/kg ip od. Treatment began 24 h after lethal intravenous challenge with Aspergillus fumigatus and continued for 5 days. Mortality occurred in eight of eight untreated control animals versus none of eight treated with ravuconazole 5 or 10 mg/kg/day or itraconazole 10 mg/kg/day. Mortality occurred in one of eight animals treated with ravuconazole 25 mg/kg/day, one of eight with amphotericin B and two of eight treated with itraconazole 5 mg/kg/day. Compared with controls, each of the antifungals examined significantly reduced the tissue burden in liver and brain, although only the highest doses of the azole drugs and amphotericin B significantly reduced tissue burden in the kidney. All three doses of ravuconazole improved survival and also reduced the tissue burden of Aspergillus. In this model of invasive aspergillosis, ravuconazole showed significant activity and may be a useful compound in human disease.