| Abstract | The efficacy of itraconazole (ITZ) solubilized in hydroxypropyl-beta-cyclodextrin (ITZ-IV) was examined in a murine model of invasive pulmonary aspergillosis (IPA). Immunosuppressed mice were infected by the intratracheal inoculation of Aspergillus fumigatus conidia (2 x 10(6) conidia/mouse). Their body weight rapidly decreased and they died within 6 days after infection. Intravenous administration of various doses of ITZ-IV was started 24 h after infection and was continued once a day for 4 days. ITZ-IV at daily doses of 10, 20, or 40 mg/kg was as effective as the intraperitoneal administration of amphotericin B (AMPH) at a dosage of 1 mg/kg daily in improving survival. ITZ-IV (20 mg/kg per day), as well as AMPH (1 mg/kg per day) significantly lowered the fungal burden in the pulmonary tissues. Histological improvement was seen within 2 days after the beginning of administration of ITZ-IV (20 mg/kg per day). In mice intravenously given a single dose of ITZ-IV (20 mg/kg), the blood level and pulmonary tissue level of ITZ plus its active metabolites, mainly hydroxyitraconazole (OH-ITZ), decreased gradually after the injection, but after 4 h their concentration was still between 1.4 microg/ml (ITZ) and 1.9 microg/ml (OH-ITZ), concentrations that were approximately 10 to 20 times greater than the minimum inhibitory concentration (MIC) of ITZ for challenging the strain of A. fumigatus (0.16 microg/ml). These results support the clinical usefulness of ITZ-IV for the treatment of IPA in immunocompromised patients. |
| Authors | Shigeru Tansho, Shigeru Abe, Hiroko Ishibashi, Shinichi Torii, Hisaya Otani, Yasuo Ono, Hideyo Yamaguchi
(Affiliation: Department of Microbiology and Immunology, University of Teikyo, School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. stansho at med.teikyo-u.ac.jp)
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| Journal | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
(J Infect Chemother)
Vol. 12
Issue 6
Pg. 355-62
(Dec 2006)
ISSN: 1341-321X Japan |
| PMID | 17235640
(Publication Type: Journal Article)
|
| Chemical References |
- Antifungal Agents
- Amphotericin B
- Itraconazole
|
| Topics |
- Amphotericin B
(administration & dosage, pharmacology)
- Animals
- Antifungal Agents
(administration & dosage, pharmacokinetics, pharmacology)
- Aspergillosis
(drug therapy, immunology)
- Aspergillus fumigatus
(pathogenicity)
- Female
- Immunocompromised Host
(drug effects)
- Infusions, Intravenous
- Infusions, Parenteral
- Itraconazole
(administration & dosage, pharmacokinetics, pharmacology)
- Lung Diseases, Fungal
(drug therapy)
- Mice
- Mice, Inbred ICR
- Models, Animal
- Neutropenia
(microbiology)
- Survival Analysis
|
