Table 2

Profiles of 14 compounds tested with the pooled preparation of human hepatocytes lot 70 and 73 and the key parameters for the in vivo prediction

No.	compound	f_u	R_B	CL_{P, in vivo}	F_{PO, in vivo}	CL_{H, int, in vivo}	D	R	CL_{int, in vitro, 70+73}	SF₇₀₊₇₃	CL_{H, predicted, 70+73}	F_{H, predicted, 70+73}
				ml/min/kg		ml/min/kg	10⁶cells/ml	after 2-h	ml/min/10⁹ cells	10⁹cells/kg	ml/min/kg
1	Naloxone	0.559	1.22^2-150	24.8	0.02	154.9	1.0	0.07 ± 0.01	18.31 ± 0.69	8.5	25.2 ± 0.0	0.01 ± 0.00
2	Buspirone	0.050	0.81^2-150	28.3 ± 10.3	0.04 ± 0.04	79.1	1.0	0.33 ± 0.01	7.66 ± 0.26	10.3	16.5 ± 0.0	0.02 ± 0.00
3	Verapamil	0.100	0.77	11.8 ± 5.0	0.20 ± 0.12	31.0	1.0	0.51 ± 0.01	4.65 ± 0.13	6.7	14.9 ± 0.1	0.07 ± 0.00
4	Lidocaine	0.296	0.84	12.5 ± 1.5	0.24 ± 0.05	29.8	1.0	0.70 ± 0.03	2.43 ± 0.26	12.3	13.4 ± 0.6	0.23 ± 0.03
5	Imipramine	0.185	1.08	11.8 ± 8.1	0.42 ± 0.08	21.8	1.0	0.77 ± 0.01	1.78 ± 0.06	12.3	13.3 ± 0.3	0.40 ± 0.01
6	Metoprolol	0.883	1.13	10.8 ± 1.5	0.50 ± 0.11	17.8	1.0	0.81 ± 0.05	1.47 ± 0.39	12.1	12.1 ± 2.0	0.49 ± 0.09
7	Timolol	0.400	0.84^2-150	7.7 ± 1.2	0.61 ± 0.06	9.1	1.0	0.91 ± 0.03	0.69 ± 0.23	13.2	6.5 ± 1.7	0.62 ± 0.10
8	Antipyrine	0.970		0.7 ± 0.1	0.96 ± 0.06	0.8	5.0	0.98 ± 0.01	0.03 ± 0.02		0.4 ± 0.2	0.98 ± 0.01
9	Diazepam	0.013	0.71	0.3 ± 0.1	0.94 ± 0.20	0.9	5.0	0.96 ± 0.02	0.05 ± 0.03		0.7 ± 0.4	0.95 ± 0.03
10	Quinidine	0.146	0.92	4.9 ± 1.6	0.70 ± 0.17	7.1	2.0	0.84 ± 0.04	0.61 ± 0.14		6.1 ± 1.2	0.68 ± 0.06
11	Caffeine	0.650		1.0 ± 0.4	0.92 ± 0.04	1.7	2.0	0.96 ± 0.01	0.13 ± 0.03		1.6 ± 0.4	0.92 ± 0.02
12	Propranolol	0.123	0.89^2-150	17.3 ± 2.0	0.32 ± 0.04	24.4	2.0	0.52 ± 0.01	2.28 ± 0.07		13.6 ± 0.2	0.26 ± 0.01
13	Diclofenac	0.003	0.55	4.1 ± 0.8	0.58 ± 0.14	6.7	2.0	0.80 ± 0.04	0.77 ± 0.17		6.2 ± 0.8	0.46 ± 0.07
14	Phenacetin	0.600	1.01^2-150	19.6 ± 4.5	0.02 ± 0.03	127.5	2.0	0.01 ± 0.00	14.72 ± 0.29		20.8 ± 0.0	0.01 ± 0.00
									average SF₇₀₊₇₃	10.8 ± 2.4

All these values were quoted from the literature as follows. Naloxone [Asali and Brown (1984); Holford (1998)]; buspirone [Gammans et al. (1986)]; verapamil [Gross et al. (1988); McAllister and Kirsten (1982); Obach (1999)]; lidocaine [Remmel et al. (1991); Wing et al. (1984)]; imipramine [the pharmacokinetics were mean value of the report of Ciraulo et al. (1988) and Nagy and Johansson (1975)]; metoprolol [Johansson et al. (1974); Regardh et al. (1974); Regardh et al. (1981)]; timolol [Wilson et al. (1982),Holford (1998)]; antipyrine [Elfstrom and Lindgren (1978); Vesell et al. (1975)]; diazepam [Divoll et al. (1983); Greenblatt et al. (1980); Maguire et al. (1980)]; quinidine [Guentert et al. (1979); Hardy and Schentag (1988); Hughes et al. (1975)]; caffeine [Blanchard (1982); Newton et al. (1981)]; propranolol [Walle et al. (1989);Wilson et al. (1982)]; diclofenac [Chan et al. (1987); Obach (1999); Willis et al. (1980)]; phenacetin [Raaflaub and Dubach (1975); Vesell et al. (1975)].

f_u, unbound fraction in plasma;R_B, blood-to-plasma concentration ratio (reported); CL_{P, in vivo}, plasma clearance in humans (reported); F_{PO, in vivo}, oral bioavailability in humans (reported); CL_{H, int, in vivo}, hepatic intrinsic clearance values calculated from F_{PO, in vivo} by the dispersion model (using the Goal Seek method attached to Microsoft Excel); D, cell density of hepatocytes suspended in serum;R, the ratio of unchanged compound concertration at 2-hr incubation to that at time 0; CL_{int, in vitro,70+73}, in vitro intrinsic clearance observed when test compounds were metabolized in the pooled preparation of Lot 70 and 73 suspended in human serum; SF₇₀₊₇₃, scaling factor calculated from CL_{int, in vitro, 70+73} / CL_{H, int, in vivo} for pooled preparation of Lot 70 and 73; CL_{H, predicted, 70+73}, predicted hepatic clearance from CL_{int, in vitro, 70+73} and average SF₇₀₊₇₃ (10.8 × 10⁹ cells/kg) as a scaling factor; F_{H, predicted, 70+73}, predicted hepatic availability from CL_{int, in vitro, 70+73} and average SF₇₀₊₇₃ (10.8 × 10⁹ cells/kg) as a scaling factor.
↵2-150 In house data.