TABLE 6

Predicted human V_ss (l/kg) by interspecies scaling and Simcyp

Drug	Predicted by V_ss,u from				Predicted by f_ut^{^a} from				Predicted by f_ut^{^b} from				Predicted by Simcyp		Obverved Human^{^c}
Drug	Rat	Dog	Monkey	Average	Rat	Dog	Monkey	Average	Rat	Dog	Monkey	Average	Method 1	Method 2	Obverved Human^{^c}
Cefotetan	0.09	0.08	0.25	0.14	0.12	0.11	0.23	0.13	0.15	0.13	0.17	0.15	0.35	0.20	0.13
Tiludronate	5.0	1.0	3.5	3.2	5.0	1.0	3.5	2.0	5.3	0.91	2.8	1.8	0.45	0.20	1.0
Captopril	1.7	2.3	6.7	3.5	1.6	2.3	6.7	2.5	1.7	1.9	5.2	2.2	1.3	0.26	0.81
Cefazolin	0.17	0.06	0.20	0.14	0.18	0.09	0.18	0.13	0.21	0.13	0.13	0.14	0.28	0.21	0.11
Cefoperazone	0.07	0.05	0.30	0.14	0.11	0.08	0.24	0.11	0.16	0.13	0.14	0.14	0.27	0.21	0.14
Diclofenac	0.40	0.13	0.10	0.21	0.43	0.15	0.11	0.16	0.48	0.16	0.13	0.16	1.9	0.21	0.17
Fluvastatin	0.44	1.6	3.7	1.9	0.46	1.6	3.7	0.95	0.53	1.2	2.9	0.94	3.6	0.25	0.42
Furosemide	0.13	0.04	0.05	0.07	0.14	0.07	0.07	0.08	0.17	0.12	0.11	0.10	0.30	0.21	0.11
Gemfibrozil	0.14	2.0	0.11	0.74	0.17	2.0	0.13	0.19	0.21	1.6	0.13	0.17	1.5	0.22	1.1
Indomethacin	4.3	6.5	3.1	4.7	4.2	6.5	3.1	4.2	4.4	5.5	2.4	3.6	1.8	0.23	0.93
Ketoprofen	0.15	0.05	0.07	0.09	0.18	0.08	0.10	0.10	0.23	0.13	0.14	0.14	0.34	0.23	0.13
Naproxen	0.07	0.09	0.10	0.09	0.10	0.10	0.10	0.10	0.15	0.10	0.10	0.10	0.29	0.20	0.10
Troglitazone	0.60	1.2	0.84	0.86	0.62	1.1	0.83	0.81	0.7	0.92	0.66	0.74	3.0	1.1	0.71
Valproic acid	0.09	0.07	0.10	0.09	0.13	0.11	0.11	0.12	0.18	0.14	0.13	0.14	0.60	0.20	0.15
Warfarin	0.26	0.05	0.13	0.15	0.27	0.09	0.12	0.12	0.29	0.13	0.11	0.11	0.38	0.20	0.11
Phenytoin	0.50	0.70	5.6	2.3	0.51	0.71	5.7	0.83	0.54	0.62	4.5	0.77	0.37	0.31	1.4
Antipyrine	1.0	0.68	0.73	0.81	1.0	0.68	0.73	0.78	0.98	0.54	0.57	0.64	0.50	0.44	0.87
Caffeine	1.0	0.66	0.68	0.79	1.0	0.66	0.69	0.76	0.98	0.55	0.55	0.63	0.48	0.42	0.73
Coumarin	0.67	3.8	3.1	2.5	0.69	3.8	3.1	1.4	0.74	3.2	2.5	1.4	0.45	0.31	2.2
Flunisolide	3.2	3.7	3.6	3.5	3.2	3.8	3.6	3.5	3.4	3.2	2.8	3.1	0.97	0.87	1.8
Isosorbide dinitrate	4.9	1.9	1.5	2.8	4.8	1.9	1.5	2.1	5.0	1.6	1.2	1.8	0.59	0.51	1.9
Isosorbide mononitrate	1.7	0.58	0.47	0.90	1.6	0.59	0.47	0.67	1.6	0.49	0.37	0.52	0.47	0.41	0.60
Lorazepam	0.63	5.4	0.69	2.2	0.65	5.5	0.71	0.94	0.70	4.6	0.60	0.87	0.72	0.57	1.3
Zidovudine	1.2	0.96	1.2	1.1	1.2	0.97	1.2	1.1	1.1	0.81	0.93	0.94	0.48	0.42	1.8
Cyclophosphamide	0.85	0.91	1.6	1.1	0.85	0.89	1.6	1.0	0.80	0.71	1.2	0.85	0.58	0.54	0.70
Felodipine	82	44	3.6	43	80	44	3.5	9.4	85	37	2.8	7.3	25	87	9.7
Lamivudine	1.7	0.94	1.1	1.3	1.7	0.93	1.1	1.2	1.7	0.75	0.89	0.96	0.52	0.50	1.3
Midazolam	0.96	1.1	0.89	0.98	0.98	1.1	0.93	0.99	1.1	0.91	0.78	0.90	2.4	2.5	1.1
Mifepristone	4.3	5.9	11	7.0	4.3	6.0	11	6.1	4.5	5.1	8.6	5.6	37	1029	1.5
Nifedipine	3.9	1.1	0.92	2.0	3.0	1.1	0.89	1.2	1.8	0.92	0.67	0.94	9.7	16	0.78
Indinavir	4.0	1.1	1.7	2.2	3.9	1.1	1.7	1.7	4.0	0.86	1.3	1.3	16	37	0.82
Amiodarone	62	5.3	4.1	24	61	5.4	4.1	6.7	65	4.5	3.3	5.5	38	2127	66
Biperiden	18	14	6.5	13	18	14	6.5	11	19	12	5.1	8.9	4.7	4.5	6.2
Bupivacaine	0.90	1.3	0.46	0.90	0.91	1.3	0.47	0.74	0.97	0.96	0.40	0.63	3.4	1.9	0.84
Chlorpromazine	56	26	3.7	29	55	26	3.7	9.2	59	22	3.0	7.4	8.7	12	11
Cimetidine	3.5	1.9	1.7	2.4	3.5	1.9	1.8	2.2	3.6	1.6	1.4	1.8	0.53	1.2	1.2
Citalopram	17	9.9	8.7	12	16	10	8.8	11	17	8.4	6.9	9.3	3.7	6.6	14
Diltiazem	3.8	17	2.0	7.4	3.7	17	2.0	3.7	3.9	14	1.6	3.1	11	14	3.1
Erythromycin	6.6	2.0	1.1	3.2	6.5	2.0	1.1	1.9	6.9	1.7	0.84	1.5	0.82	2.1	0.89
Haloperidol	11	17	4.8	11	11	17	4.8	8.3	11	14	3.8	7.0	6.2	9.1	18
Hydrodolasetron	19	8.7	26	18	18	8.8	26	14	19	7.3	20	13	3.7	2.0	11
Imipramine	9.3	4.9	9.0	7.7	9.2	5.0	9.0	7.1	9.7	4.2	7.1	6.2	4.6	6.0	13
Lidocaine	2.0	1.5	0.72	1.4	2.0	1.5	0.73	1.2	2.1	1.3	0.60	0.99	1.2	2.0	1.1
Metoprolol	5.4	4.6	2.4	4.2	5.4	4.6	2.4	3.7	5.6	3.9	1.9	3.1	0.82	2.5	4.2
Propafenone	6.3	5.6	4.5	5.5	6	5.6	4.5	5.4	7	4.7	3.6	4.6	2.4	1.2	2.2
Propranolol	4.0	2.4	5.6	4.0	3.9	2.4	5.6	3.5	4.2	2.0	4.4	3.1	2.0	1.6	3.6
Venlafaxine	9.6	3.3	3.5	5.5	9.4	3.3	3.5	4.3	9.8	2.8	2.7	3.6	2.8	1.1	4.4
Verapamil	3.4	5.2	4.0	4.2	3.4	5.2	4.0	4.1	3.6	4.4	3.2	3.6	4.6	3.2	3.7
Disopyramide	4.6	1.7	1.9	2.7	4.5	1.7	1.9	2.2	4.8	1.4	1.5	1.9	1.5	2.4	0.78
Imatinib	10	7.8	12	10	10	7.8	12	9.8	11	6.6	9.7	8.6	1.7	6.2	3.9
Irinotecan	3.7	3.3	1.8	2.9	3.7	3.2	1.8	2.6	3.9	2.5	1.4	2.2	3.9	6.2	3.8
Nicardipine	2.0	1.5	1.1	1.5	1.9	1.5	1.1	1.4	2.0	1.2	0.89	1.2	18	38	0.64
Nicotine	4.7	3.3	1.5	3.2	4.7	3.3	1.5	2.5	4.8	2.8	1.2	2.0	0.66	0.92	2.6
Quinidine	5.9	7.7	1.6	5.1	5.9	7.7	1.5	3.1	6.2	6.4	1.1	2.4	1.6	3.6	3.0
Vinblastine	17	7.1	1.7	8.7	17	7.0	1.7	3.7	18	5.7	1.3	2.9	38	1625	24
Cefpiramide	0.02	0.03	0.18	0.07	0.06	0.07	0.14	0.07	0.11	0.12	0.09	0.13	0.26	0.66	0.11
Ciprofloxacin	6.5	2.5	2.6	3.8	6.4	2.5	2.6	3.2	6.6	2.1	2.0	2.6	0.93	0.43	2.3
Doxorubicin	49	62	26	45	48	62	26	40	51	52	20	34	0.39	13	25
Gabapentin	1.4	0.16	0.68	0.76	1.4	0.15	0.68	0.31	1.4	0.10	0.53	-0.22	0.73	0.76	0.82
Lamifiban	0.25	0.79	0.27	0.44	0.25	0.79	0.27	0.33	0.15	0.63	0.22	0.40	0.52	0.90	0.29
Levofloxacin	3.4	1.1	1.7	2.1	3.4	1.1	1.7	1.7	3.5	0.94	1.3	1.4	1.3	4.2	1.2
Methotrexate	0.20	0.36	0.70	0.42	0.23	0.37	0.72	0.35	0.25	0.33	0.60	0.33	0.33	0.24	0.67
Morphine	2.6	3.8	12	6.3	2.6	3.8	12	4.1	2.7	3.2	9.7	3.8	0.52	1.4	3.3
Naltrexone	3.6	14	4.1	7.2	3.5	14	4.1	5.0	3.7	12	3.2	4.5	1.7	4.8	7.6
Telmisartan	0.86	0.45	0.58	0.63	0.88	0.49	0.61	0.62	0.97	0.47	0.53	0.58	4.3	0.40	5.3
Topotecan	1.8	5.9	1.5	3.1	1.7	5.8	1.5	2.1	1.6	4.6	1.2	1.7	0.49	1.2	1.8
Verlukast	0.19	0.01	0.12	0.11	0.22	0.05	0.14	0.07	0.28	0.11	0.17	0.12	0.31	0.23	0.11

↵a Equation 2.
↵b Equation 3.
↵c See Table 2 for source of in vivo data.