Table 1

Kinetic parameters for UK-103,320 formation

MicrosomesMetabolite Formation
Human liver microsomes, Mean ± S.E. for n = 4 livers
  K m (μM)14.4  ± 2.0
  K s (μM)164.7  ± 15.1
Expressed human cytochromes, Fitted function values ± asymptotic S.E.
 CYP3A
  V max 1.9  ± 0.2
  K m (μM)23.1  ± 7.5
  K s (μM)918.7  ± 411.9
V max/K m ratio (% of total)79.1%
 CYP2C9
  V max 0.2  ± 0.006
  K m (μM)9.6  ± 1.2
  V max/K m ratio (% of total)20.0%
 CYP2C19
  V max 0.02  ± 0.003
  K m (μM)23.1  ± 13.0
  V max/K m ratio (% of total)0.83%
 CYP2D61-150

Because standards were not available, absolute units were not assigned to Vmax values. However, since the role of each cytochrome has been determined relative to the others,Vmax values for microsomes containing cDNA-expressed enzymes are expressed in relative units (chromatographic peak height ratios) and their Vmax/Km values have been normalized for the relative hepatic abundance of each cytochrome.

  • 1-150 , Data points could not be fit to Michaelis-Menten kinetics. However, CYP2D6 does not appear to account for greater than 2% of sildenafil biotransformation.