TABLE 5

Enzyme kinetic parameters of abrocitinib metabolism in human liver microsomes using Michaelis-Menten substrate inhibition modeling

Kinetic ParameterM1M2/M3M4Total
Km, µM143 ± 20251 ± 26519 ± 100
Vmax, pmol/min per mg26.7 ± 2.273.8 ± 5.0881 ± 125
Ki, µM1480 ± 3161680 ± 3201340 ± 430
CLint, µL/min per mg0.1870.2941.72.18
CLint,app,sc, mL/min per kg0.1760.2781.62.05
Fractional proportion CLint,app,sc0.0860.1360.780
  • Data expressed as the mean plus or minus standard error of mean from triplicate replicates; unbound fraction (fu,inc) of abrocitinib in human liver microsomes (0.3 mg/mL) was 1.

  • fu,inc, unbound fraction; Ki, inhibition constant for substrates exhibiting substrate inhibition kinetics; Vmax, maximum rate of metabolism.