TABLE 1

Steady-state kinetic constants for R-, S-, and rac-warfarin reduction by human liver cytosol

SubstrateMetaboliteBest-Fit ModelaVmax (pmol/min/mg protein)Km (µM)Efficiency (Vmax/Km)
R-warfarinRS-warfarin alcoholMichaelis-Menten155 ± 18710 ± 1600.22
RR-warfarin alcoholMichaelis-Menten0.63 ± 0.18560 ± 3300.0011
S-warfarinSR-warfarin alcoholNAbNAbNAbNAb
SS-warfarin alcoholMichaelis-Menten41 ± 183500c0.012
Rac-warfarinAlcohol 2 (RS/SR-warfarin alcohols)Michaelis-Menten78 ± 10710 ± 1700.11
Alcohol 1 (RR/SS-warfarin alcohols)Michaelis-Menten4.8 ± 0.7330 ± 1300.015
Rac-warfarin (Malátková et al., 2016)Alcohol 2 (RS/SR-warfarin alcohols)Michaelis-Menten76.4 ± 6.0746 ± 930.10
Alcohol 1 (RR/SS-warfarin alcohols)Michaelis-Menten2.0 ± 0.2248 ± 510.0080
  • NA, not applicable.

  • a Best fit of data was determined between hyperbolic (Michealis-Menten) and nonhyperbolic (Hill equation) models using extra sum-of-squares F test in GraphPad Prism.

  • b SR-warfarin alcohol was consistently quantifiable only at S-warfarin concentrations of 600 µM or greater, yet data could not be reliably fit to any kinetic model.

  • c The predicted Km was greater than the highest substrate concentration used in this study (1000 μM) owing to solubility limits; thus, there is more error in the kinetic constants than predicted by a fit, hence the exclusion of S.E. from the table.