Drug interactions of micafungin <I>in vitro</I>

DOI 6 Citations 10 References
  • Kaneko Hayato
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
  • Yamato Yasuhiro
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
  • Hashimoto Tomoko
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
  • Ishii Ikuko
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
  • Shiraga Toshifumi
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
  • Kawamura Akio
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
  • Terakawa Masato
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
  • Kagayama Akira
    Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.

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  • <I>In vitro</I>におけるmicafunginの薬物相互作用

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Abstract

The in vitro drug interactions of micafungin (MCFG), a new echinocandin-like lipopeptide antifungal agent, were evaluated using human serum and human liver microsomes and the following results were obtained.<BR>1. The percent of MCFG bound to human serum proteins was as high as 99.74%. Warfarin, diazepam, salicylic acid and methotrexate did not affect the protein binding of MCFG.<BR>2. Based on the results at the concentrations ranging from 0.1 to 1 mmol/L (130-1, 300 μg/mL) of MCFG, the binding constant (KD) of MCFG at the bilirubin binding site was calculated to be 2.0×103 L/mol, indicating that MCFG has a lower affinity to the bilirubin binding site than salicylic acid (5.0×103L/mol) or sulfisoxazole (1.4×104L/mol).<BR>3. M 5 and M 13 formation activities significantly correlated with the activities of coumarin 7-hydroxylase and testosterone 6, β-hydroxylase. M 13 formation activity also significantly correlated with the activities of tolbutamide methyl-hydroxylase and S-mephenytoin 4'-hydroxylase.<BR>4. The metabolism of MCFG was inhibited by tranylcypromine and ketoconazole (KCZ). The 50% inhibitory concentration (IC50) of cyclosporin A, tacrolimus and KCZ for the metabolic activity of MCFG was > 100, > 100 and 6.2 μmol/L, respectively.<BR>5. The IC50 of MCFG, fluconazole (FLCZ) and KCZ for the metabolic activity of terfenadine was 67.7, >100 and 0.46 μmol/L, respectively, and 24.9, 0.12 and 44.2 μmol/L for astemizole. The inhibition constant of MCFG, FLCZ and KCZ for the metabolic activity of nifedipine was 17.3, 0.012 and 10.7μmol/L, respectively.<BR>6. The IC50 of MCFG, caspofungin acetate and KCZ for the metabolic activity of cyclosporin A was 31, 39 and 0.14 μmol/L, respectively.

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