TABLE 3

Comparison of in vivo human intrinsic clearance with in vitro intrinsic clearance using the relay method

Compounds	Metabolizing Enzymes	Human In Vivo Intrinsic Clearance	Relay Method Intrinsic Clearance ± S.E.^{^a}	Fold Difference between In Vitro and In Vivo
		ml · min⁻¹ · kg⁻¹	ml · min⁻¹ · kg⁻¹
Diazepam	CYP3A, CYP2C19	15 (Hallifax et al., 2010)	15 ± 0.85	1.0
Disopyramide	CYP3A	5.9 (Obach et al., 2008)	4.8 ± 0.55	1.2
Theophylline	CYP1A2	2.6 (Hallifax et al., 2010)	2.8 ± 0.60	1.1
Timolol	CYP2D6	36–49 (Obach et al., 2008; Hallifax et al., 2010)	14 ± 2.5	2.6
Tolbutamide	CYP2C9	4.9 (Brown et al., 2007)	7.4 ± 0.40	1.5
S-Warfarin	CYP3A, CYP2C9	4.5 (Hallifax et al., 2010)	4.2 ± 0.65	1.1
Zolmitriptan	CYP1A2, MAO	13 (Obach et al., 2008)	3.5 ± 0.90^{^b}	3.7^{^b}

↵a n = 4 for all the compounds, with the exception of theophylline (n = 2) and zolmitriptan (n = 3).
↵b Underprediction of in vivo clearance could potentially be due to extrahepatic contribution of MAO.