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. Author manuscript; available in PMC: 2013 Nov 17.
Published in final edited form as: Clin Pharmacol Ther. 2011 Nov 2;91(3):442–449. doi: 10.1038/clpt.2011.178

Table 2. Fluconazole effects on metabolic kinetic parameters of 1’-hydroxymidazolam and 4-hydroxymidazolam formation for recombinant CYP3A4.

Each value represents the mean ± S.E. of the parameter estimate.

Fluconazole (µM) 0 3 10 30 100
1’-OH-MDZ (0.4–240 µM) kcat (pmol/min/pmol CYP3A4) 23.6 ± 0.9a 21.1 ± 0.4* 20.7 ± 0.4* 18.5 ± 0.5* 15.2 ± 0.6*
Km (µM) 3.6 ± 0.5a 3.5 ± 0.4 6.3 ± 0.6* 12.0 ± 1.4* 30.4 ± 4.1*
Ki (µM) 1480 ± 615a
CLint (µl/min/pmol CYP3A4) 6.55 6.03 3.29 1.54 0.50

4-OH-MDZ (0.4–240 µM) kcat (min−1) 20.2 ± 1.0 20.8 ± 0.7 21.9 ± 1.0 23.1 ± 1.2 20.9 ± 2.0
Km (µM) 28.1 ± 4.7 33.4 ± 3.6 49.5 ± 6.2* 85.3 ± 10.9* 139.0 ± 26.9*
CLint (µl/min/pmol CYP3A4) 0.72 0.62 0.44 0.27 0.15

CLint, 1’-OH/CLint, 4-OHb 9.1 9.7 7.5 5.7 3.3
a

substrate inhibition kinetics model was fit to the data.

b

CLint is calculated as the ratio of mean values of kcat and Km (CLint = kcat/Km).

*

p<0.05 compared with control (absence of fluconazole). 1’-OH MDZ, 1’-hydroxymidazolam; 4-OH MDZ, 4-hydroxymidazolam