Table 1

In vitro-in vivo correlation of seven compounds using 10 individually prepared cryopreserved human hepatocytes and key parameters for in vivo prediction

No.	compound	f_u	R_B	CL_{P, in vivo}	F_{PO, in vivo}	CL_{H, int, in vivo}	CL_{int, in vitro, mean}	SF_mean	CL_{H, predicted, mean}	F_{H, predicted, mean}	CL_{H, predicted, biol}	F_{H, predicted, biol}
				ml/min/kg		ml/min/kg	ml/min/10⁹cells	10⁹ cells/kg	ml/min/kg		ml/min/kg
1	Naloxone	0.559	1.22^1-150	24.8	0.02	154.9	34.7 ± 8.2	4.5	25.3 ± 0.1	0.00 ± 0.00	23.8 ± 0.7	0.06 ± 0.03
2	Buspirone	0.050	0.81^1-150	28.3 ± 10.3	0.04 ± 0.04	79.1	12.1 ± 6.9	6.5	16.2 ± 0.6	0.04 ± 0.03	13.2 ± 1.9	0.22 ± 0.11
3	Verapamil	0.100	0.77	11.8 ± 5.0	0.20 ± 0.12	31.0	7.3 ± 3.6	4.3	14.5 ± 0.9	0.09 ± 0.05	10.6 ± 1.9	0.34 ± 0.12
4	Lidocaine	0.296	0.84	12.5 ± 1.5	0.24 ± 0.05	29.8	2.3 ± 0.7	12.9	10.6 ± 1.9	0.39 ± 0.11	5.5 ± 1.4	0.68 ± 0.08
5	Imipramine	0.185	1.08	11.8 ± 8.1	0.42 ± 0.08	21.8	1.5 ± 0.6	14.5	8.6 ± 2.7	0.61 ± 0.12	4.0 ± 1.4	0.82 ± 0.06
6	Metoprolol	0.883	1.13	10.8 ± 1.5	0.50 ± 0.11	17.8	2.3 ± 0.8	7.8	12.0 ± 2.5	0.49 ± 0.10	5.8 ± 1.6	0.75 ± 0.07
7	Timolol	0.400	0.84^1-150	7.7 ± 1.2	0.61 ± 0.06	9.1	1.0 ± 0.6	9.0	6.0 ± 2.8	0.65 ± 0.16	2.7 ± 1.4	0.84 ± 0.08
							average SF_mean	8.5 ± 4.0

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; [Wing et al. (1984), Remmel et al. (1991)]; imipramine [the pharmacokinetics were mean value of the report of Nagy and Johansson (1975) and Ciraulo et al. (1988)]; metoprolol [Johansson et al. (1974); Regardh et al. (1974); Regardh et al. (1981)]; timolol [Wilson et al. (1982), [Holford (1998].

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 th dispersion model (using the Goal Seek method attached to Microsoft Excel); CL_{int, in vitro, mean}, in vitro intrinsic clearance observed when test compounds were metabolized by 10 individual lots of human hepatocytes suspended in human serum; SF_mean, mean of scaling factor calculated from CL_{int, in vitro, mean}/ CL_{H, int, in vivo} for 10 individual lots; CL_{H, predicted, mean}, predicted hepatic clearance from CL_{int, in vitro, mean} and average SF_mean (8.5 × 10⁹ cells/kg) as a scaling factor;F_{H, predicted, mean}, predicted hepatic availability from CL_{int, in vitro, mean} and average SF_mean (8.5 × 10⁹ cells/kg) as a scaling factor; CL_{H, predicted, biol}, predicted hepatic clearance from CL_{int, in vitro, mean} and biologically based scaling factor of hepatocellularity (SF_biol = 3.1 × 10⁹cells/kg); F_{H, predicted, biol}, predicted hepatic availability from CL_{int, in vitro, mean} and biologically based scaling factor of hepatocellularity (SF_biol = 3.1 × 10⁹ cells/kg).
↵1-150 In house data.