TABLE 7

CL_int 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-CL_int), mean ISEF value for CYP2C9, CYP2D6, and CYP3A4 using multiple substrates. ISEF method 2: ISEF determined on the basis of substrate depletion (ISEF-CL_int) 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.

Compound	CL_int Measured in HLM	CL_int Extrapolated Using ISEF
Compound	CL_int Measured in HLM	Method 1	Method 2	Method 3	Method 4
A	30	15	21	33	32
B	39	24	30	47	44
C	14	17	24	37	36
D	60	43	60	95	92
E	13	18	25	38	37
F	20	24	33	52	50
G	27	38	49	74	70
H	15	28	37	57	52
I	41	47	64	100	96
J	89	67	91	141	135
K	26	25	34	52	50
L	11	9	12	19	19
M	67	71	97	152	146
N	5	11	14	22	21
O	309	230	312	485	466
P	33	30	32	50	48
Metoprolol	9	13	11	24	17
Carbamazepine	0	5	6	9	8
Fluoxetine	27	38	31	58	41
Sildenafil	221	229	310	486	466
Tolterodine	260	201	199	366	296
Harmine	238	197	174	219	154
R²		0.966	0.901	0.888	0.821
Average fold error		1.03	1.26	1.95	1.79
MRS		−7.8	5.2	48	37
RMSE		14	29	49	57