Table 3

Contribution of CYP3A4 to the overall metabolic clearance of R (+)- and S (−)-gallopamil estimated by RAF in human liver microsomes

Human Liver Microsomes	RAF^3-a	CL_CYP3A4^3-b		CL_HLM		Contribution^3-c
Human Liver Microsomes	RAF^3-a	R (+)	S (−)	R(+)	S (−)	R (+)	S (−)
		ml/min/mg		%
HL-31	2.55	0.273	0.125	0.307	0.232	89	54
HL-32	1.77	0.190	0.087	0.212	0.173	90	50
HL-33	3.90	0.418	0.191	0.518	0.387	81	49
HL-34	3.45	0.369	0.169	0.442	0.274	84	62
HL-35	1.77	0.190	0.087	0.140	0.092	136	95
HL-37	0.97	0.104	0.047	0.113	0.051	92	93
HL-38	4.48	0.480	0.220	0.581	0.314	83	70
HL-39	1.61	0.173	0.079	0.235	0.149	73	53
HL-40	3.00	0.321	0.147	0.328	0.170	98	87
Mean	2.61	0.280	0.128	0.320	0.205	92	68
S.D.	1.18	0.126	0.058	0.165	0.107	18	19

The clearances of gallopamil enantiomers by recombinant CYP3A4 (CL_rec-CYP3A4) were 0.107 and 0.049 ml/min/mg for R(+)- and S (−)-gallopamil, respectively.

↵3-a The RAF values for CYP3A4 were calculated as described in Materials and Methods.
↵3-b The clearance values for CYP3A4 (CL_CYP3A4) were estimated as follows: CL_CYP3A4 = CL_rec-CYP3A4 × RAF.
↵3-c Expressed as percentage of CL_CYP3A4 in the first order rate clearance by human liver microsomes (CL_HLM) for substrate disappearance in each microsomal preparation.