title: In vitro and in vivo efficacies of the new triazole albaconazole against Cryptococcus neoformans.
abstract: 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 micro g/ml, with the MICs for most isolates being between 0.039 and 0.156 micro g/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 micro g/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.
authors.affiliation: Department of Medicine, Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Miller
authors.forename: W A
authors.initials: WA
authors.lastname: Schell
authors.forename: E A
authors.initials: EA
authors.lastname: Wills
authors.forename: D L
authors.initials: DL
authors.lastname: Toffaletti
authors.forename: M
authors.initials: M
authors.lastname: Boyce
authors.forename: D K
authors.initials: DK
authors.lastname: Benjamin
authors.forename: J
authors.initials: J
authors.lastname: Bartroli
authors.forename: J R
authors.initials: JR
authors.lastname: Perfect
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D003455:Cryptococcus neoformans / Q000187:drug effects*; D015725:Fluconazole / Q000627:therapeutic use; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use*; D011817:Rabbits; D016019:Survival Analysis; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D011799:Quinazolines; D014230:Triazoles; D015725:Fluconazole; C112424:albaconazole