TABLE 3

RAF-scaled CL_int and ICR values of losartan, meloxicam, and sildenafil using RAF values derived from various combinations of probe substrate for CYP2C9 and CYP3A4

Drug	CYP3A4 Probe Substrate	CYP2C9 Probe Substrate
		Diclofenac			Tolbutamide			S-Warfarin
		RAF-Scaled CL_int^{^a}	Measured CL_int^{^b}	ICR^{^c}	RAF-Scaled CL_int	Measured CL_int	ICR	RAF-Scaled CL_int	Measured CL_int	ICR
		min⁻¹	min⁻¹		min⁻¹	min⁻¹		min⁻¹	min⁻¹
Losartan	Midazolam	0.0149	0.0042	3.5	0.0132	0.0042	3.1	0.0141	0.0042	3.3
	Nifedipine	0.0127	0.0042	3.0	0.0110	0.0042	2.6	0.0118	0.0042	2.8
	Testosterone	0.0032	0.0042	0.8	0.0015	0.0042	0.4	0.0024	0.0042	0.6
Meloxicam	Midazolam	0.0140	0.0004	39.1	0.0130	0.0004	36.3	0.0135	0.0004	37.7
	Nifedipine	0.0117	0.0004	32.8	0.0107	0.0004	30.0	0.0112	0.0004	31.4
	Testosterone	0.0024	0.0004	6.6	0.0014	0.0004	3.9	0.0019	0.0004	5.2
Sildenafil	Midazolam	1.1028	0.2663	4.1	1.0923	0.2663	4.1	1.0975	0.2663	4.1
	Nifedipine	0.8988	0.2663	3.4	0.8883	0.2663	3.3	0.8936	0.2663	3.4
	Testosterone	0.0530	0.2663	0.2	0.0425	0.2663	0.2	0.0477	0.2663	0.2

↵^a RAF-scaled CL_int = ∑(CL_int,u × RAF); based on CL_int,u values of rP450 in Table 2 and RAF values in Table 1.
↵^b Measured CL_int based on CL_int,u values of HLMs in Table 2.
↵^c ICR = RAF-scaled CL_int/measured CL_int.