TABLE 3

Assessment of in vivo CYP2C19 and CYP3A4 inhibition risk by OMP and metabolites

Because substrate concentration was <K_m for all IC₅₀ experiments, the IC₅₀ was assumed to be equivalent to K_i. [I]/IC₅₀ and λ/k_deg values are calculated based on in vitro inhibitory parameters shown in Table 2. Either total or unbound C_max were used for inhibitor concentration. N.D., not detected.

Target P450	Inhibitor	Reversible ([I]/K_i)^a		Irreversible (λ/k_deg)
Target P450	Inhibitor	C_max	C_max*f_u	C_max	C_max*f_u
CYP2C19 (hepatic)	OMP	0.080	0.0042	5.2	0.29
	OH-OMP	0.012	0.0022	N.D.	N.D.
	DM-OMP	0.0008	0.0008	0.12	0.12
	OMP-S	0.028	0.0007	0.92	0.022
	COMP	N.D.	N.D.	N.D.	N.D.
	Total	0.12	0.0078	6.25	0.44
CYP3A4 (hepatic)	OMP	0.017	0.0009	1.23	0.065
	OH-OMP	0.024	0.004	N.D.	N.D.
	DM-OMP	0.002	0.002	0.11	0.11
	OMP-S	0.017	0.0004	N.D.	N.D.
	COMP	0.005	0.0004	N.D.	N.D.
	Total	0.066	0.0074	1.34	0.18
CYP3A4 (intestinal)	OMP	6.0	6.0	50	50

↵a [I]/K_i is extrapolated from the [I]/IC₅₀ ratio.