Table 2

Pharmacokinetic parameters and K_m values for the metabolism of the compounds tested

No.	Compound	K_mValue^2-a	f_ub	R_B	i.v. Dose	CL_p	In Vivo CL_H, int^2-c	F_po
		μM			mg/kg	ml/min/kg
1	Alprenolol	9.5		1.71^2-b	2	79	148	0.04
2	Chlorpromazine		0.10	1.48^2-b	4	76	162
3	Diazepam	3	0.22	1.04	1.5	52	108	0.35
4	7-Ethoxy coumarin	0.8	0.22	0.98	(infusion)	48	97
5	Hexobarbital	105	0.62	1.00	25	62	195	0.18
6	Lidocaine	1.7^2-a	0.38	1.27	10	88	591	0.01
7	Phenytoin	4.6	0.18	0.99	10	13	15	0.26
8	Propranolol		0.075	0.78	1.5	62		0.08
9	Quinidine	2.6^2-a	0.20	1.87	5	93	193
10	Verapamil		0.054	0.85	1	40	78	0.06
11	Compound X		0.038^2-b		1	32^2-b	46	0.46^2-b
12	Compound Y		0.067^2-b		1	36^2-b	56	0.10^2-b
13	Antipyrine	2200	1.00	1.00	20	3.6	3.7	0.74
14	Caffeine	150	0.90		2.5	13	14	1.00
15	Ibuprofen	70^2-a	0.02		2.5	2.8	2.9	0.90
16	Tolbutamide	650	0.031	0.75	13	0.5	0.5	0.90
17	Theophylline		0.72		3.25	3.7	3.8	1.00
18	(S)-Warfarin	32	0.0112		2 (s.c.)	0.18	0.18

All values were quoted from the literature as follows: alprenolol (Borg et al., 1974; Skanberg, 1980); chlorpromazine (Sato and Koshiro, 1995a,b); diazepam (Igari et al., 1984; Tsang and Wilkinson, 1982;Zomorodi et al., 1995); 7-ethoxy coumarin (Carlile et al., 1998); hexobarbital (Igari et al., 1982; Rane et al., 1977; Sawada et al., 1985; Van der Graaff et al., 1985; Vermeulen et al., 1991); lidocaine (Kawai et al., 1985; Nakamoto et al., 1997; Shibasaki et al., 1988;Supradist et al., 1984); phenytoin (Ashforth et al., 1995; Colburn and Gibaldi, 1977; Scriba et al., 1995; Tsuru et al., 1982); propranolol (Iwamoto and Watanabe, 1985; Singh et al., 1991; Terao and Shen, 1983); quinidine (Rakhit and Mico, 1985; Watari et al., 1989); verapamil (Bhatti and Foster, 1997; Manipisitkul and Chiou, 1993); antipyrine (Buters and Reichen, 1990; Pollack et al., 1984; Singh et al., 1991;Torres-Molina et al., 1992); caffeine (Bonati et al., 1984, 1985; Hayes et al., 1995); ibuprofen (Kata and Tekle, 1992; Satterwhite and Boudinot, 1991); tolbutamide (Ashforth et al., 1995; Sugita et al., 1981; Yamao et al., 1994); theophylline (Gomita et al., 1991; Matthew and Houston, 1990; Ramzan and Levy, 1987); (S)-warfarin (Baars et al., 1990; Pohl et al., 1976).

↵2-a K_m values were obtained from incubation with hepatocytes except for Nos. 6, 9, and 15, which were obtained from microsomal incubation.
↵2-b In-house data.
↵2-c In vivo CL_H, int was calculated by the dispersion model assuming that hepatic clearance was the same as CL_p. No. 8 was calculated to be infinite because the CL_p value was greater than the hepatic blood flow rate.