TABLE 2

Physicochemical properties, plasma protein binding (f_up), blood plasma concentration ratio (R_B), and volume of distribution at steady state for the test compounds (V_ss)

Physicochemical properties were calculated using ACD Labs Chemistry version 12. The source for in vitro and in vivo data is as follows. Values for f_up were determined for the present work, except where noted and reference included.

Drug	Physicochemical Property				f_up				R_B	V_ss				V_ss Source
Drug	Class	clogP	cpKa1	cpKa2	Rat	Dog	Monkey	Human	Human	Rat	Dog	Monkey	Human	V_ss Source
										l/kg
Cefotetan	A	1.3	1.7	2.6	0.41	0.48	0.10	0.15	0.65^{^s}	0.25	0.25	0.17	0.13	^{^a}
Tiludronate	A	2.0	1.1	2.6	0.30	0.30	0.20	0.10	0.60^{^z}	15	3.0	7.0	1.0	^{^a}
Captopril	A	2.0	3.6		0.73	0.78	0.38	0.71	0.70^{^s}	1.7	2.5	3.6	0.81	^{^a}
Cefazolin	A	−0.7	2.6		0.13	0.43	0.058	0.091	0.64^{^s}	0.23	0.27	0.13	0.11	^{^a}
Cefoperazone	A	−1.1	2.6		0.36	0.38	0.029	0.066	0.64^{^s}	0.39	0.28	0.13	0.14	^{^a}
Diclofenac	A	4.6	4.2		0.008	0.007	0.007	0.004	0.71^{^b}	0.75	0.23	0.17	0.17	^{^a}
Fluvastatin	A	4.6	4.3		0.016	0.003	0.007	0.007	0.70^{^s}	1.0	0.7	3.7	0.42	^{^a}
Furosemide	A	2.3	3.0		0.013	0.062	0.025	0.010	0.70^{^b}	0.16	0.23	0.11	0.11	^{^a}
Gemfibrozil	A	4.3	4.8		0.010^{^b}	0.004^{^b}	0.007^{^b}	0.005^{^b}	0.75^{^b}	0.28	1.6	0.16	1.1	^{^b}
Indomethacin	A	4.3	4.0		0.003	0.006	0.004	0.007	0.98^{^b}	1.9	5.6	1.8	0.93	^{^b}
Ketoprofen	A	2.9	4.2		0.011^{^b}	0.024^{^b}	0.014^{^b}	0.004^{^b}	1.1^{^b}	0.42	0.28	0.25	0.13	^{^b}
Naproxen	A	2.9	4.8		0.008	0.004	0.003	0.003	0.55^{^x}	0.18	0.12	0.10	0.10	^{^a}
Troglitazone	A	4.7	6.3		0.010	0.004	0.005	0.006	0.55^{^w}	1.0	0.77	0.71	0.71	^{^a}
Valproic acid	A	2.6	4.8		0.37	0.22	0.080	0.052	0.58^{^w}	0.66	0.31	0.15	0.15	^{^a}
Warfarin	A	3.1	4.5		0.005	0.033	0.005	0.006	0.59^{^s}	0.22	0.28	0.11	0.11	^{^a}
Phenytoin	A, pKa >7	1.4	8.3		0.17	0.19	0.19	0.13	0.61^{^w}	0.64	1.0	7.8	1.4	^{^a}
Antipyrine	N	0.4			0.69	0.65	0.73	0.72	1.0^{^x}	0.97	0.62	0.74	0.87	^{^a}
Caffeine	N	−0.6			0.70	0.90	0.95	0.78	1.0^{^v}	0.92	0.76	0.83	0.73	^{^a}
Coumarin	N	1.4			0.32	0.28	0.24	0.17	1.1^{^s}	1.3	6.5	4.5	2.2	^{^a}
Flunisolide	N	2.0			0.22	0.24	0.26	0.24	0.76^{^s}	3.0	3.7	4.0	1.8	^{^a}
Isosorbide dinitrate	N	1.0			0.55	0.87	0.62	0.55	1.5^{^s}	4.9	3.0	1.7	1.9	^{^a,^d}
Isosorbide mononitrate	N	−0.2			0.42	1.0	0.77	0.72	1.0^{^s}	0.97	0.80	0.50	0.60	^{^a}
Lorazepam	N	2.4			0.090^{^b}	0.073^{^b}	0.10^{^b}	0.057^{^b}	1.1^{^b}	1.0	7.0	1.2	1.3	^{^b}
Zidovudine	N	0.1			0.73^{^b}	0.82^{^b}	0.71^{^b}	0.70^{^b}	1.1^{^b}	1.2	1.1	1.2	1.8	^{^b}
Cyclophosphamide	B, pKa <7	0.7	2.8		0.76	0.62	0.66	0.81	0.96^{^s}	0.80	0.70	1.3	0.70	^{^a}
Felodipine	B, pKa <7	4.8	2.7		0.005	0.006	0.021	0.034	0.70^{^w}	12	7.8	2.2	9.7	^{^k}
Lamivudine	B, pKa <7	−0.5	4.2		1.0	0.88	1.0	0.95	1.0^{^u}	1.8	0.87	1.2	1.3	^{^a}
Midazolam	B, pKa <7	3.8	6.0		0.028	0.011	0.035	0.011	0.55^{^w}	2.5	1.1	2.9	1.1	^{^e,^f,^g,^d}
Mifepristone	B, pKa <7	6.2	5.5		0.013	0.023	0.039	0.013	1.0^{^u}	4.3	10.5	33	1.5	^{^k,^y}
Nifedipine	B, pKa <7	3.6	2.7		0.004	0.13	0.065	0.12	0.59^{^x}	0.13	1.2	0.5	0.78	^{^k}
Indinavir	B, pKa <7	3.4	5.2	4.9	0.25	0.30	0.40	0.45	1.0^{^u}	2.2	0.73	1.5	0.82	^A,d
Amiodarone	B	7.8	9.4		0.058	0.043	0.062	0.050	0.73^{^w}	72	4.6	5.1	66	^{^k}
Biperiden	B	4.3	9.3		0.11	0.096	0.077	0.14	0.95^{^v}	14	9.5	3.6	6.2	^{^k}
Bupivacaine	B	3.3	8.1		0.23	0.061	0.23	0.16	0.68^{^v}	1.3	0.51	0.66	0.84	^{^h,ⁱ,^j,^d}
Chlorpromazine	B	5.2	9.4		0.062	0.073	0.26	0.12	1.2^{^v}	29	16	8.0	11	^{^k}
Cimetidine	B	0.6	7.1		0.69	0.72	0.85	0.75	0.97^{^w}	3.3	1.8	2.0	1.2	^{^p,^q,^r,^d}
Citalopram	B	3.5	9.6		0.40	0.32	0.37	0.32	1.3^{^s}	21	10	10	14	^{^a}
Diltiazem	B	4.7	8.9		0.21	0.28	0.38	0.22	1.0^{^v}	3.6	21	3.5	3.1	^{^k}
Erythromycin	B	1.9	8.2		0.48	0.45	0.30	0.34	0.91^{^s}	9.3	2.7	0.93	0.89	^{^a}
Haloperidol	B	3.8	8.0		0.12	0.29	0.18	0.13	1.1^{^v}	10	37	6.6	18	^{^k}
Hydrodolasetron	B	2.8	8.8		0.20	0.28	0.27	0.25	1.0^{^u}	15	9.6	28	11	^{^a}
Imipramine	B	4.4	9.5		0.15	0.16	0.14	0.13	1.1^{^v}	11	6.0	9.7	13	^{^b}
Lidocaine	B	2.2	8.0		0.38	0.44	0.42	0.31	0.87^{^v}	2.5	2.1	0.98	1.1	^{^a}
Metoprolol	B	1.6	9.4		0.80	0.61	0.77	0.62	1.1^{^v}	7.0	4.5	3.0	4.2	^{^a}
Propafenone	B	3.4	9.3		0.077	0.088	0.18	0.099	0.70^{^v}	4.9	5.0	8.2	2.2	^{^m,^o,^k,^d}
Propranolol	B	2.9	9.5		0.28	0.20	0.21	0.21	0.80^{^v}	5.3	2.3	5.6	3.6	^{^a,^l}
Venlafaxine	B	2.5	9.3		0.69	1.0	1.0	1.0	1.0^{^u}	6.6	3.3	3.5	4.4	^C,d
Verapamil	B	4.0	9.0		0.20	0.19	0.19	0.17	0.84^{^v}	4.0	5.8	4.5	3.7	^{^m,ⁿ,^k,^d}
Disopyramide	B	2.3	10.1	4.5	0.61	0.62	0.48	0.45	1.0^{^w}	6.2	2.3	2.0	0.78	^{^a}
Imatinib	B	2.9	7.6	3.0	0.030	0.12	0.063	0.097	1.1^{^s}	3.2	9.2	8.0	3.9	^{^s,^t,^d}
Irinotecan	B	3.7	9.3	5.1	0.19	0.067	0.26	0.22	1.2^{^s}	3.2	1.0	2.1	3.8	^{^a}
Nicardipine	B	4.9	7.3	2.6	0.014	0.019	0.038	0.021	0.71^{^v}	1.3	1.3	1.9	0.64	^{^a}
Nicotine	B	0.9	8.0	3.2	1.0	1.0	1.0	1.0	0.8^{^u}	4.7	3.3	1.5	2.6	^{^a}
Quinidine	B	2.8	9.3	4.8	0.17	0.11	0.059	0.17	0.96^{^v}	6.0	4.8	0.55	3.0	^{^a}
Vinblastine	B	5.9	7.9	5.6	0.13	0.059	0.16	0.18	1.0^{^u}	12	2.3	1.5	24	^{^a}
Cefpiramide	Z	0.2	3.5	8.7	0.31	0.30	0.010	0.018	0.65^{^s}	0.26	0.45	0.10	0.11	^{^a}
Ciprofloxacin	Z	1.6	6.4	8.7	0.57	1.0	0.56	0.80	0.75^{^w}	4.6	3.1	1.8	2.3	^{^a}
Doxorubicin	Z	0.2	7.4	8.7	0.067	0.092	0.12	0.13	2.0^{^u}	25	44	24	25	^{^a}
Gabapentin	Z	1.1	4.7	10.3	1.0	1.0	1.0	1.0	1.0^{^u}	1.4	0.16	0.68	0.82	^{^a}
Lamifiban	Z	−0.3	3.4	10.8	0.92^{^c}	0.89^{^c}	∼1.0^{^u}	0.94^{^c}	1.0^{^u}	0.24	0.75	0.29	0.29	^{^c}
Levofloxacin	Z	1.9	5.2	7.4	0.83^{^b}	0.92^{^b}	0.87^{^b}	0.78^{^b}	1.5^{^b}	3.6	1.3	1.9	1.2	^{^b}
Methotrexate	Z	−0.5	3.5	5.6	0.41	0.31	0.36	0.21	1.0^{^u}	0.4	0.54	1.2	0.67	^{^a}
Morphine	Z	0.9	9.5	8.3	0.70	0.67	0.61	0.63	1.0^{^v}	2.9	4.0	12	3.3	^{^a}
Naltrexone	Z	2.1	9.2	7.5	0.57	0.46	0.72	0.58	1.2^{^s}	3.5	11	5.1	7.6	^{^a,^d}
Telmisartan	Z	6.5	3.9	5.0	0.007^{^b}	0.018^{^b}	0.008^{^b}	0.003^{^b}	1.2^{^b}	2.0	2.7	1.5	5.3	^{^b}
Topotecan	Z	0.3	8.9	7.7	0.21	0.17	0.88	0.72	1.0^{^u}	0.52	1.4	1.8	1.8	^B,d
Verlukast	Z	3.4	4.3	2.2	0.003	0.012	0.002	0.0007	1.0^{^u}	0.81	0.24	0.33	0.11	^D,E

A, acid; N, neutral; B, base; Z, zwitterions; zwitterions pKa1, acid; zwitterions pKa2, base.
↵a Jolivette and Ward, 2005;
↵b Deguchi et al., 2011;
↵c Lave et al., 1996;
↵d Obach et al., 2008;
↵e Gueorguieva et al., 2004;
↵f Kuroha et al., 2002;
↵g Nishimuta et al., 2010;
↵h Wu et al., 2010;
↵i Mazoit et al., 1988;
↵j Thompson et al., 1986;
↵k Evans et al., 2006;
↵l Hayes and Cooper, 1971;
↵m Poulin and Theil, 2002;
↵n Bai et al., 1993;
↵o Puigdemont et al., 1987;
↵p Kaka et al., 1989;
↵q Viernstein et al., 1990;
↵r Tahara et al., 2006;
↵s Amgen data on file;
↵t Ishizuka et al., 2007;
↵u Assumed value;
↵v Rogers and Rowland, 2007;
↵w Uchimura et al., 2010;
↵x Brown et al., 2007;
↵y V_z/F reported for humans by Liu et al. (1988);
↵z Sansom et al., 1995; ^A Lin et al., 1996; ^B Ahlawat et al., 2008; ^C Howell et al. 1994; ^D Tocco et al., 1990; ^E Depré et al., 1992.