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

Abstract

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.

• Authors: William R Kirkpatrick, Sofia Perea, Brent J Coco, Thomas F Patterson
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 49 Issue 2 Pg. 353-7 (Feb 2002) ISSN: 0305-7453 [Print] England
• PMID: 11815579 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Thiazoles
• Triazoles
• ER 30346

Topics

• Animals
• Antifungal Agents (pharmacology, therapeutic use)
• Aspergillosis (drug therapy, microbiology, mortality)
• Aspergillus fumigatus (drug effects, isolation & purification)
• Disease Models, Animal
• Drug Evaluation, Preclinical (methods, statistics & numerical data)
• Guinea Pigs
• Humans
• Male
• Organ Culture Techniques
• Organ Specificity (drug effects)
• Thiazoles (pharmacology, therapeutic use)
• Triazoles (pharmacology, therapeutic use)