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Antimicrobial Agents and Chemotherapy, February 2004, p. 384-387, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.384-387.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Efficacies of the New Triazole Albaconazole against Cryptococcus neoformans

J. L. Miller,1 W. A. Schell,1 E. A. Wills,1 D. L. Toffaletti,1 M. Boyce,1 D. K. Benjamin Jr.,2 J. Bartroli,3 and J. R. Perfect1*

Department of Medicine, Pediatrics,1 Duke Clinical Research Institute, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina,2 Drug Discovery, J. Uriach & Cia, Palau-solità i Plegamans, Barcelona, Spain3

Received 23 July 2003/ Returned for modification 2 October 2003/ Accepted 14 October 2003

The activity of albaconazole (UR-9825; J. Uriach & Cía. S.A., Barcelona, Spain) was compared to that of fluconazole against 12 isolates of Cryptococcus neoformans in vitro and against 1 isolate in vivo in a rabbit model of cryptococcal meningitis. Albaconazole was 100-fold more potent in vitro than fluconazole on a per-weight basis and was fungicidal at potentially relevant concentrations for two isolates. MICs ranged from <=0.0012 to 1.25 µg/ml, with the MICs for most isolates being between 0.039 and 0.156 µg/ml. Isolates were from human immunodeficiency virus (HIV)-infected and non-HIV-infected patients and were of serotypes A, B, and C; and the fluconazole MICs for some of the isolates were elevated. Infected rabbits were treated with either fluconazole or albaconazole at dosages ranging from 5 to 80 mg/kg of body weight/day. The peak concentrations of albaconazole in serum and cerebrospinal fluid (CSF) averaged 4.14 and 0.62 µg/ml, respectively, in animals receiving 80 mg/kg/day. Comparison of the concentrations in serum and CSF suggested a level of CSF penetration of approximately 15%. Despite limited penetration into the subarachnoid space, at all three doses tested albaconazole was as effective as fluconazole for the treatment of cryptococcal meningitis in rabbits.

* Corresponding author. Mailing address: P.O. Box 3353, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-4016. Fax: (919) 684-8902. E-mail: perfe001{at}mc.duke.edu.

Antimicrobial Agents and Chemotherapy, February 2004, p. 384-387, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.384-387.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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