Table 1

Enzyme kinetic parameters of ezlopitant metabolism by rat, guinea pig, dog, monkey, and human liver microsomes

Species	Reaction	K_Mapp	V_max	CL′_int
		μM	pmol/min/mg microsomal protein	ml/min/mg microsomal protein
Rat	Ezlopitant metabolism	2.8	693	0.248
	CJ-12,458 formation	9.4	154	0.016
	CJ-12,764 formation	2.5	480	0.192
	RRT = 0.900 formation	4.1	73	0.018
Guinea pig	Ezlopitant metabolism	2.5	972	0.389
	CJ-12,458 formation	7.1	279	0.039
	CJ-12,764 formation	1.9	537	0.283
	RRT = 0.616 formation	93	1383	0.015
Dog	Ezlopitant metabolism^1-a	0.3	5	0.016
		55	250	0.005
	CJ-12,458 formation	19.5	29	0.0015
	CJ-12,764 formation^1-a	0.3	5	0.017
		52	153	0.003
Monkey	Ezlopitant metabolism	2.3	5833	2.54
	CJ-12,458 formation	10.4	2523	0.243
	CJ-12,764 formation	2.3	3787	1.65
	RRT = 0.616 formation	14.1	100	0.007
		164	5103	0.031
Human	Ezlopitant metabolism	98	735	0.0077
	CJ-12,458 formation	80	324	0.0041
	CJ-12,764 formation	89	257	0.0029
	RRT = 0.616 formation	270	180	0.0007

Reaction velocities were measured as described in Experimental Procedures. Kinetic parameters were determined by fitting reaction velocity versus substrate concentration data to the Michaelis-Menten equation. In the case of dog, the data was fit to a sum equation of two Michaelis-Menten terms.

↵1-a Two K_Mvalues were determined for dog ezlopitant metabolism and CJ-12,764 formation.