TABLE 5

Input parameters used in predicting hepatic clearance of pevonedistat using ECM

ParametersCLint
(µl/min/106 cells)
Predicted CLint
(ml/min/kg)
Observed Renal CL (L/h)Predicted Plasma CL (CCM) (L/h)Predicted Plasma CL (ECM) (L/h)Observed
Plasma CL (L/h)
Passive efflux (CLdiff,eff)2.98.70.830.8
(ESF 4)
32.1
(ESF 13)
32.2
Active uptake CL (CLact,inf)7.121
Intrinsic metabolic CL (CLint,met)51.1a43.7
Intrinsic biliary CL (CLint,bile)ND15.1b
Active efflux (CLact,eff)NDND
Passive diffusion CL (CLdiff,inf)2.98.7
  • ND, not determined.

  • a Unit is µl/min/mg of microsomal protein.

  • b Biliary CL was backcalculated from in vivo metabolism and mass balance data.