Table 1

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

μM pmol/min/mg microsomal protein ml/min/mg microsomal protein
RatEzlopitant metabolism2.86930.248
CJ-12,458 formation9.41540.016
CJ-12,764 formation2.54800.192
RRT = 0.900 formation4.1730.018
Guinea pigEzlopitant metabolism2.59720.389
CJ-12,458 formation7.12790.039
CJ-12,764 formation1.95370.283
RRT = 0.616 formation9313830.015
DogEzlopitant metabolism1-a 0.350.016
CJ-12,458 formation19.5290.0015
CJ-12,764 formation1-a 0.350.017
MonkeyEzlopitant metabolism2.358332.54
CJ-12,458 formation10.425230.243
CJ-12,764 formation2.337871.65
RRT = 0.616 formation14.11000.007
HumanEzlopitant metabolism987350.0077
CJ-12,458 formation803240.0041
CJ-12,764 formation892570.0029
RRT = 0.616 formation2701800.0007

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 KMvalues were determined for dog ezlopitant metabolism and CJ-12,764 formation.