Evaluation of antifungal activity of an antifungal drug by in vitro simulation of in vivo pharmacokinetics of the drug against fungal hyphal growth.
An automatic drug concentration simulator (DCS) has been developed and its applicability has been demonstrated by in vitro simulation of the human plasma concentration-time curve of fluconazole (FLCZ) against hyphal growth of Candida albicans and Aspergillus fumigatus. The response of hyphal growth to FLCZ was continually monitored and analyzed using an automatic hyphal growth analyzing system (Bio-Cell Tracer). The simulated concentration of FLCZ by DCS was confirmed by HPLC. The DCS assay was reproducible with a mean coefficient of variation (C.V., n=3) of 5.38 %. When the growth of C. albicans hyphae was tested, there was a lag of onset of FLCZ effect between the time when FLCZ concentration became maximal (C MAX, 7.95 microg/ml ) and the point at which hyphal growth ceased. In contrast, FLCZ was found inactive against A. fumigatus. The newly devised technique could provide clinicians with important information in determining optimal dosing regimens for antifungal drugs.
Department of Biotechnology, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei, Tokyo 184-8588, Japan.
K B
KB
Oh
H
H
Shirogane
H
H
Matsuoka
A
A
Niitsu
S
S
Yamada
H
H
Kurata
M
M
Mochizuki
H
H
Kume
D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000254:growth & development*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development*; D015725:Fluconazole / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans
D000935:Antifungal Agents; D015725:Fluconazole