TABLE 1

Ki (micromolar) estimates for ketoconazole, itraconazole, and fluconazole obtained in human liver pooled microsomes using midazolam, testosterone, quinidine, and nifedipine as probes Ki values for ketoconazole and itraconazole were corrected for the microsomal fraction unbound (0.71 and 0.056, respectively) at the protein concentration used in the study (0.25 mg/ml).


Probe Substrate

Inhibitor
Ketoconazole
Itraconazole
Fluconazole
Midazolam 0.059 ± 0.003 0.50 ± 0.04 11.9 ± 0.9
Testosteronea 0.17 ± 0.01 0.23 ± 0.02 27.6 ± 2.1
Quinidine 0.053 ± 0.004 0.32 ± 0.08 13 ± 1
Nifedipineb
0.52 ± 0.19
3.12 ± 0.71
86 ± 3
  • a Three-site kinetic model defined in Galetin et al. (2002), α = 0.09 to 0.13

  • b γ/δ ratio is 0.2, 0.3, and 0.67 for ketoconazole, itraconazole, and fluconazole, respectively