TABLE 1

CB, maximum daily dose, and C_max of the tested compounds

Test compounds (10 μM) were incubated with human liver microsomes in the presence of NADPH (first arm), NADPH and UDPGA (second arm), or NADPH, UDPGA, and GSH (third arm) or with hepatocytes (fourth arm). The CB amounts were determined with duplicate incubations. Daily dose and C_max represent the maximum daily dose and the maximum concentration at the maximum daily dose, respectively. Daily dose and C_max are from the package inserts or the following references: 1) Maass et al., 1982; 2) Durand et al., 1992; 3) Boni et al., 1997; 4) Greene and Barbhaiya, 1997; 5) Fontana et al., 1998; 6) Kalgutkar and Soglia, 2005; 7) Walgren et al., 2005; and 8) Lammert et al., 2008.

Compound	CB				Daily Dose	C_max	Reference
Compound	1st	2nd	3rd	4th	Daily Dose	C_max	Reference
	pmol/mg protein				mg/day	ng/ml
Positive compounds
Acetaminophen	179	124	28	16	4000	82,400^{^a}	6, 7
Alpidem	440	192	88	101	150	65.7^{^a}	2, 6, 7
Bromfenac	51	107	44	22	100	9240^{^a}	3, 6, 7, 8
Carbamazepine	119	90	35	18	1200	9000^{^a}	6, 7
Diclofenac	120	173	59	49	200	3320^{^a}	6, 7, 8
Flutamide	477	471	225	35	750	78.0^{^a}	6, 7
Imipramine	271	258	63	10	300	280^{^a}	6
Nefazodone	1364	997	306	254	600	2760^{^a}	4, 6, 7, 8
Tacrine	264	201	47	14	200	78.5^{^a}	5, 6, 7, 8
Ticlopidine	1286	1136	249	60	500	1950	6, 7
Tienilic acid	538	487	124	28	500	57,000	1, 6, 7, 8
Troglitazone	1170	967	273	118	600	2820	6, 7
Negative compounds
Acetylsalicylic acid	N.D.	N.D.	N.D.	3	300	1840
Caffeine	3	4	2	1	900	9000^{^b}
Dexamethasone	445	272	262	41	20	20.9^{^a}
Ibuprofen	N.D.	N.D.	N.D.	2	600	49,800^{^a}
Losartan	105	105	40	19	100	801
Paroxetine	235	182	24	19	50	26.9^{^a}
Pioglitazone	236	302	59	11	45	2100^{^a}
Rosiglitazone	1189	894	229	11	8	598
Sertraline	49	42	26	16	200	142
Theophylline	N.D.	N.D.	N.D.	1	400	6000^{^a}
Venlafaxine	5	5	6	2	225	225^{^a}
Zolpidem	23	14	8	6	10	120	2

N.D., CB for test compounds was lower than that for the control without NADPH and UDPGA.
↵a C_max value normalized by dose.
↵b C_max value normalized by body weight.