T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations
| Autor: | H Hayakawa, Harumi Araki, N Annen, S Yamamoto, Y Watanbe, K Shimizu, Hirokazu Narita, Akira Yotsuji, K Fujimaki, N Nishida, H Imaizumi, Ritsuko Hori |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Male
Antifungal Agents Itraconazole Microgram Antifungal drug Hydroxybutyrates Microbial Sensitivity Tests Biology Pharmacology Aspergillosis Mice Dogs Pharmacokinetics Oral administration medicine Animals Pharmacology (medical) Fluconazole Candida Mice Inbred ICR Aspergillus fumigatus Candidiasis Triazoles medicine.disease Rats Infectious Diseases Cryptococcus neoformans Systemic candidiasis Rabbits medicine.drug Research Article |
| Popis: | T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 microgram/ml; fluconazole; 0.148 microgram/ml; and itraconazole, 0.0170 microgram/ml. For Cryptococcus neoformans the GM-IC80s were as follows: T-8581, 9.28 micrograms/ml; fluconazole, 4.00 micrograms/ml; and itraconazole, 0.119 microgram/ml. For Aspergillus fumigatus the GM-IC80s were as follows: T-8581, 71.0 micrograms/ml; fluconazole, 239 micrograms/ml; and itraconazole, 0.379 microgram/ml. Against systemic candidiasis in mice, the 50% effective doses (ED50s) of T-8581, fluconazole, and itraconazole (given orally) were 0.412, 0.392, and > 320 mg/kg of body weight, respectively. Against systemic aspergillosis in mice, the ED50s of T-8581, fluconazole, and itraconazole (given orally) were 50.5, 138, > 320 mg/kg, respectively. T-8581 was also efficacious when it was given parenterally (ED50, 59.2 mg/kg), while the ED50 of fluconazole given parenterally was > 20 mg/kg. Against systemic aspergillosis in rabbits, T-8581 was more effective than fluconazole and itraconazole in prolonging the life span. The high concentrations of T-8581 were observed in the sera of mice, rats, rabbits and dogs. Species differences in half-lives and areas under the concentration-time curves were observed, with the values for mice, rats, rabbits, and dogs increasing in that order. These results suggest that T-8581 would be a potentially effective antifungal drug for oral and parenteral use. |
| Databáze: | OpenAIRE |
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