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JAC Advance Access published online on May 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg261
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Improving the mouse model for studying the efficacy of voriconazole

John R. Graybill 1*, Laura K. Najvar 1, Gloria M. Gonzalez 2, Steve Hernandez 1, Rosie Bocanegra 1

1 The University of Texas Health Science Center at San Antonio, Department of Medicine, Division of Infectious Diseases (7881), 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
2 The University of Texas Health Science Center at San Antonio, Department of Medicine, Division of Infectious Diseases (7881), 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, N.L., Mexico

* Corresponding author. E-mail: jrgraybill{at}aol.com.

Received 19 February 2003 ; accepted 12 March 2003

Abstract

Outbred ICR mice were rendered neutropenic, infected intravenously with Fusarium solani and treated orally with voriconazole. When given alone, voriconazole was not protective up to 40 mg/kg/day. When grapefruit juice was administered before infection, mice were protected by voriconazole. The mechanism may be inhibition of gut mucosal cytochrome enzymes that rapidly degrade voriconazole in the mouse. These murine studies support expansion of voriconazole therapy in other highly resistant systemic mycoses.

Keywords: voriconazole, mice, grapefruit juice
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