Open AccessEffect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs
Author(s) -
Sakaeda Toshiyuki,
Iwaki Koichi,
Kakumoto Mikio,
Nishikawa Mika,
Niwa Toshiro,
Jin Jiangshu,
Nakamura Tsutomu,
Nishiguchi Kohshi,
Okamura Noboru,
Okumura Katsuhiko
Publication year - 2005
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/0022357056118
Subject(s) - ketoconazole , miconazole , pharmacology , itraconazole , azole , cyp3a4 , fluconazole , micafungin , chemistry , candida glabrata , drug interaction , cytochrome p450 , drug , medicine , biology , microbiology and biotechnology , biochemistry , candida albicans , antifungal , enzyme
The effects of micafungin on cytochrome P450 3A4 (CYP3A4) metabolic and multidrug resistance protein 1 (MDR1) transport activities were investigated and compared with those of amphotericin B and four azole antifungal drugs (ketoconazole, itraconazole, fluconazole and miconazole). The effects on the metabolic activity of CYP3A4 were examined by measuring nifedipine oxidase activity in human liver microsomes and the effects on MDR1 transport activity were evaluated using [ 3 H]digoxin in MDR1‐overexpressing LLC‐GA5‐COL150 cells. An inhibitory effect on CYP3A4 activity was found for ketoconazole, itraconazole and miconazole, with 50% inhibitory concentrations of 11.7, 32.6 and 74.2 nM, respectively. Fluconazole and micafungin had only slight inhibitory effects and amphotericin B had no effect. The MDR1‐mediated transport of [ 3 H]digoxin was inhibited by ketoconazole and itraconazole, and slightly by miconazole. It is suggested that micafungin and amphotericin B would be unlikely to cause drug‐drug interactions by inhibition of CYP3A4 and MDR1. A positive correlation between the inhibitory effects on CYP3A4 and MDR1 activities was observed, and the physicochemical mechanisms involved and impact on clinical treatment should be studied further.