TABLE 6

Prediction of AUC changes for letrozole in the presence of increasing concentrations of t-CA

Predictions are based on mechanism-based inhibition parameters determined in human liver microsomes.

	AUC Fold Increase
f_m	k_deg = 0.00061 min⁻¹ (t_1/2 = 19 hours)	k_deg = 0.00031 min⁻¹ (t_1/2 = 37 hours)	Range
0.01 µM [t-CA]
0.80	1.04	1.08	1.01–1.08
0.31	1.01	1.01
0.1 µM [t-CA]
0.80	1.37	1.66	1.06–1.66
0.31	1.06	1.11
1 µM [t-CA]
0.80	2.97	3.61	1.27–3.61
0.31	1.27	1.34
10 µM [t-CA]
0.80	4.47	4.71	1.41–4.71
0.31	1.41	1.43
100 µM [t-CA]
0.80	4.76	4.87	1.44–4.87
0.31	1.44	1.45