Comparative study on the efficacy of liposomal amphotericin B and voriconazole in a murine pulmonary aspergillosis model.
BACKGROUND
No clinical studies have compared the efficacy of liposomal formulation AMB (L-AMB) and voriconazole (VRC) in the treatment of pulmonary aspergillosis. The aim of this study was to compare the efficacy of L-AMB and VRC in murine pulmonary aspergillosis.


METHODS
Leucopenic mice were infected intratracheally with Aspergillus fumigatus and treated intravenously with L-AMB (once a day) or VRC (twice a day).


RESULTS
L-AMB and VRC at a dose of >or=5 and >or=20 mg/kg, respectively, significantly prolonged the survival time of infected mice and reduced the pulmonary fungal burden in comparison with the control group. At the maximum recommended dose for clinical use, 5 mg/kg of L-AMB exhibited greater efficacy than 10 mg/kg of VRC, which achieved an area under the concentration-time curve level equivalent to that of 6 mg/kg (loading dose) in humans, in terms of increasing survival and reducing the fungal burden.


CONCLUSIONS
The in vivo efficacy of L-AMB was superior to that of VRC at the maximum recommended dose in a murine pulmonary aspergillosis model.
Takemoto
Koji
K
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Konohana-ku, Osaka, Japan. koji-takemoto@ds-pharma.co.jp
Yamamoto
Yutaka
Y
Ueda
Yutaka
Y
Kanazawa
Katsunori
K
Yoshida
Koichiro
K
Niki
Yoshihito
Y
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001232:Aspergillus fumigatus / Q000302:isolation & purification; D004195:Disease Models, Animal; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D055732:Pulmonary Aspergillosis / Q000188:drug therapy*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C068538:liposomal amphotericin B; D000666:Amphotericin B; D065819:Voriconazole