TABLE 1

Compound properties, responsible drug metabolizing enzyme and observed proteinbinding and in vivo CL for the 12 test compounds

	Ion Class	MW	LogD_7.4	Main Responsible Enzyme	In Vivo CL_p	fu_b	fu_inc	Observed In Vivo CL_int
					ml/min/kg			ml/min/kg
Low CL_int compounds
S-Warfarin	Neutral	308.3	0.2	2C9 > 3A4	0.06^{^a}	0.018^{^a}	0.953	0.06
Diazepam	Neutral	284.7	2.8	2C19 > 3A4	0.5^{^a}	0.036^{^a}	0.808	0.5
Disopyramide	Base	339..5	−0.2	3A4	0.9^{^b}	0.16^{^b}	0.827	0.9
Metoprolol	Base	267.4	−0.4	2D6	13^{^b}	0.88^{^b}	0.922	1.4
Theophylline	Neutral	180.2	−0.05	1A2	1.3^{^a}	0.53^{^a}	0.956	37.1
AZ01	Base	374.4	1.5	3A4	na
AZ02	Acid	475.5	1.9	3A4	2.1	0.039	0.893	4.7
Intermediate to high CL_int compounds with diverse enzymology
Ketoprofen	Acid	254.3	−0.3	UGT2B2	1.2^{^a}	0.17^{^a}	0.956	2.4
Sildenafil	Base	474.6	2.5	2C9/2C19/3A4	6.0^{^a}	0.094^{^a}	0.892	8.6
Carvedilol	Base	406.5	3.1	2D6 > 2C9	8.7^{^a}	0.030^{^a}	0.434	15.4
Imipramine	Base	280.4	2.3	2C9 > 2D6 > 3A4 > 1A2	13.5^{^a}	0.13^{^a}	0.127	41.5
Ketanserin	Base	395.4	3.0	AKR/CR	6.7^{^b}	0.094^{^b}	0.752	10.1