TABLE 1

Prediction of CL_{int ub in vivo} using rat hepatocytes for 36 AZ compounds

Compound	Charge	logD_7.4	fu_inc	f_medium	Predicted CL_{int ub in vivo}					Observed CL_{int ub in vivo}
Compound	Charge	logD_7.4	fu_inc	f_medium						Observed CL_{int ub in vivo}	Conventional	AUC_0-∞	Disappearance Rate
						ml/min/kg			ml/min/kg
AZ1	Acid	0.6	0.93	0.04	27, 78	360, 700	7000, 3600	3000
AZ2	Acid	1.2	0.84	0.10	42, 27	440, 260	6400, 3800	3100
AZ3	Acid	1.8	0.95	0.11	37, 44	160, 100	2200, 3300	3500
AZ4	Acid	1.3	0.88	0.10	74, 77	540, 190	4500, 2300	15,000
AZ5	Acid	3.0	0.60	0.16	170, 110	510, 180	4500, 4400	6200
AZ6	Acid	1.5	0.86	0.43	50 ± 2.9	150 ± 55	1400 ± 700	1200
AZ7	Acid	2.4	0.72	0.70	360, 270	380, 290	380, 290	380
AZ8	Acid	2.2	0.76	0.75	200 ± 150	240 ± 170	390 ± 260	830
AZ9	Acid	1.7	0.83	0.81	72, 85	60, 110	65, 110	190
AZ10	Acid	1.1	0.90	0.84	50, 41	75, 38	75, 39	210
AZ11	Acid	2.0	0.79	0.29	190, 83	490, 210	2000, 1500	10,000
AZ12	Acid	1.3	0.88	0.24	79, 64	290, 200	2000, 1300	5800
AZ13	Acid	1.7	0.83	0.20	170, 90	680, 340	2400, 2300	16,000
AZ14	Acid	2.2	0.77	0.08	52, 120	360, 600	2200, 3100	4600
AZ15	Acid	0.7	0.93	0.40	27, 30	65, 50	840, 580	810
AZ16	Acid	−0.3	0.97	0.35	10, 42	55, 60	590, 600	790
AZ17	Neutral	3.5	0.47	0.06	170, 510	2200, 1000	2200, 1000	4900
AZ18	Base	1.8	0.81	0.30	380, 230	1400, 660	4500, 2900	12,000
AZ19	Zwitterion	0.7	0.93	0.65	11, 7	35, 27	35, 27	340
AZ20	Zwitterion	1.1	0.90	0.07	210, 130	1200, 600	2300, 1400	4400
AZ21	Zwitterion	1.4	0.87	0.23	16 ± 1.2	110 ± 100	1000 ± 340	630
AZ22	Zwitterion	1.0	0.90	0.33	55, 68	120, 140	390, 1100	2500
AZ23	Zwitterion	1.4	0.87	0.25	17, 35	80, 100	600, 730	3500
AZ24	Zwitterion	0.4	0.94	0.10	31 ± 5.6	340 ± 62	2800 ± 2700	3700
AZ25	Zwitterion	1.7	0.83	0.35	48, 34	95, 141	910, 1800	3700
AZ26	Zwitterion	1.4	0.87	0.35	23, 9.8	75, 100	640, 360	1200
AZ27	Zwitterion	0.2	0.95	0.45	15 ± 8.9	23 ± 24	390 ± 210	480
AZ28	Zwitterion	1.5	0.86	0.35	23, 13	40, 80	580, 440	1600
AZ29	Zwitterion	1.4	0.86	0.33	52, 42	140, 130	370, 670	1100
AZ30	Zwitterion	0.8	0.92	0.32	22, 17	75, 85	200, 220	220
AZ31	Zwitterion	1.1	0.90	0.45	11, 8	30, 50	250, 220	1100
AZ32	Zwitterion	0.6	0.93	0.30	28 ± 10	42 ± 32	710 ± 280	1200
AZ33	Zwitterion	1.2	0.84	0.43	12, 12	45, 60	200, 130	240
AZ34	Zwitterion	1.9	0.81	0.37	16, 19	50, 110	520, 360	1100
AZ35	Zwitterion	1.3	0.88	0.37	11 ± 6	57 ± 29	250 ± 10	570
AZ36	Zwitterion	2.3	0.75	0.34	27, 37	65, 120	750, 1700	2900

Data represent individual experiments or mean ± S.D. of three experiments.