TABLE 2

Summary of in vitro predicted CL_H values for 21 low- and intermediate-cleared drugs derived from three individual experiments using UHH of donor 151-03

Values for each experiment are presented as mean ± S.D. of triplicate (n = 3) incubations per compound. Prediction fold errors were calculated from the mean values and used to assess accuracy and bias.

	Compound	Predominant CYP450 Isoform	fu_p	Observed In Vivo CL_nonrenal	In Vitro Predicted CL_H Expt. 1			Fold Error	In Vitro Predicted CL_H Expt. 2			Fold Error	In Vitro Predicted CL_H Expt. 3			Fold Error
				(mL/min/kg)	(mL/min/kg)				(mL/min/kg)				(mL/min/kg)
Low nonrenal CL_b (<5 mL/min/kg)	Alprazolam⁽¹⁾	3A4	0.29	0.76	0.70	±	0.07	0.92	0.67	±	0.06	0.88	0.76	±	0.07	1.00
	Prednisolone⁽²⁾	3A4	0.28	1.44	1.55	±	0.04	1.08	1.27	±	0.05	0.88	1.95	±	0.05	1.35
	Diazepam⁽³⁾	2C19	0.015	0.53	9.02	±	0.13	17.0	8.29	±	0.16	15.6	9.39	±	0.28	17.7
	Voriconazole⁽⁴⁾	2C19	0.42	3.72	7.15	±	0.19	1.92	5.74	±	0.17	1.54	6.70	±	0.12	1.80
	Tolbutamide⁽⁵⁾	2C9	0.058	0.36	0.71	±	0.03	1.97	0.35	±	0.06	0.97	0.63	±	0.03	1.75
	Meloxicam⁽⁶⁾	2C9	0.006	0.12	0.11*^†	±	0.02	1.17	0.24^†	±	0.10	2.00	0.11*^†	±	0.02	0.92
	Warfarin⁽⁷⁾	2C9	0.01	0.08	0.22	±	0.01	2.75	0.24	±	0.02	3.00	0.36	±	0.02	4.50
	Glimepiride⁽⁸⁾	2C9	0.005	1.12	1.91	±	0.11	1.70	1.80	±	0.04	1.61	2.28	±	0.09	2.04
	Theophylline⁽⁹⁾	1A2	0.41	1.13	n.d				n.d.				n.d
	Riluzole⁽¹⁰⁾	1A2	0.02	3.20	5.32	±	0.05	1.66	6.48	±	0.09	2.03	6.78	±	0.02	2.12
	Oxazepam⁽¹¹⁾	UGT2B15	0.045	1.43	1.93	±	0.07	1.35	1.85	±	0.10	1.29	1.96	±	0.08	1.37


Intermediate nonrenal CL_b (5–15 mL/min/kg)	Midazolam⁽¹²⁾	3A4	0.02	8.61	11.0	±	0.19	1.28	10.1	±	0.22	1.17	10.9	±	0.12	1.21
	Atazanavir⁽¹³⁾	3A4	0.14	5.58	2.03	±	0.23	0.36	1.32	±	0.12	0.24	1.83	±	0.24	0.33
	Diclofenac⁽¹⁴⁾	2C9	0.005	7.60	2.12	±	0.07	0.28	1.69	±	0.09	0.22	1.64	±	0.09	0.22
	Lidocaine⁽¹⁵⁾	1A2	0.30	10.7	10.5	±	0.2	0.98	10.1	±	0.12	0.94	11.0	±	0.03	1.03
	Risperidone⁽¹⁶⁾	2D6	0.11	7.82	3.00	±	0.16	0.38	2.42	±	0.07	0.31	3.70	±	0.26	0.47
	Flecainide⁽¹⁷⁾	2D6	0.39	5.82	0.15^†	±	0.01	0.03	0.13^†	±	0.01	0.02	0.22^†	±	0.04	0.04
	Atomoxetine⁽¹⁸⁾	2D6	0.013	7.05	3.02	±	0.02	0.43	2.62	±	0.06	0.37	3.13	±	0.17	0.44
	Metoprolol⁽¹⁹⁾	2D6	0.89	11.9	0.37	±	0.10	0.03	0.30	±	0.03	0.03	0.49	±	0.05	0.04
	Imipramine⁽²⁰⁾	2D6/1A2	0.13	11.8	n.t.				4.58	±	0.11	0.39	6.45	±	0.18	0.55
	Ondansetron⁽²¹⁾	2D6	0.73	6.75	n.t.				1.73	±	0.12	0.26	2.27	±	0.13	0.34

CL_b, blood clearance; fu_p, fraction unbound in plasma; n.d., not determinable; n.t., not tested; *n = 2 replicates; ^†R² < 0.7.