TABLE 7 CLint measured in HLM and extrapolated from rhP450 data using ISEF determined by different methods
Compounds delineated by letters are internal compounds. ISEF method 1: ISEF determined on the basis of substrate depletion (ISEF-CLint), mean ISEF value for CYP2C9, CYP2D6, and CYP3A4 using multiple substrates. ISEF method 2: ISEF determined on the basis of substrate depletion (ISEF-CLint) of single substrate for CYP2C9 (diclofenac), CYP2D6 (bufuralol), and CYP3A4 (midazolam). ISEF method 3: ISEF determined on the basis of metabolite formation enzyme kinetics, VISEF. ISEF method 4: ISEF determined on the basis of metabolite formation enzyme kinetics, CLISEF.