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

^asubstrate inhibition kinetics model was fit to the data.

^bCL_int is calculated as the ratio of mean values of k_cat and K_m (CL_int = k_cat/K_m).

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