Efficacy of ravuconazole (BMS-207147) in a guinea pig model of disseminated aspergillosis.
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.
Kirkpatrick
William R
WR
Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7881, San Antonio, TX 78229-3900, USA. kirkpatrick@uthscsa.edu
Perea
Sofia
S
Coco
Brent J
BJ
Patterson
Thomas F
TF
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000302:isolation & purification; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000706:statistics & numerical data; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D009928:Organ Specificity / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use*
D000935:Antifungal Agents; D013844:Thiazoles; D014230:Triazoles; C104066:ER 30346