TABLE 2

Comparison of enzyme kinetic parameters for CYP3A4- and CYP3A5-catalyzed metabolite formation


Substrate

TST

ERM

MDZ

MDZ

FLZ

FLZ

CBZ

DXM

TFN

LDC
Metabolite 6β-OH* N-desmethyl* 1′-OH* 4-OH 3-OH* Desmethyl 10,11-Epoxide* 3-MM* Alcohol* MEGX*
CYP3A4
Best model fit Sigmoid Hyperbolic Hyperbolic Hyperbolic Sigmoid Hyperbolic Sigmoid Biphasic Inhibition Biphasic
Vmax (pmol/min/pmol) 12.2 (5) 1.45 (4.5) 5.18 (1) 1.35 (3) 19.3 (9) 0.550 (5) 4.87 (5) 0.838 (31) 0.859 (4) 3.99 (11)
S50/Km (μM) 66.9 (9) 14.7 (14) 2.82 (5) 8.44 (8) 106 (17) 35.6 (11) 248 (9) 56.2 (40) 0.501 (17) 78.9 (18)
Hill coefficient 1.33 (6) 1.21 (4) 1.75 (9)
Ksi (μM) 287 (21)
Vmax2 (pmol/min/pmol) 12.1 (30) 33.9 (18)
Km2 (μM) 2989 (48) 5927 (32)
CYP3A5
Best model fit Sigmoid Hyperbolic Hyperbolic Inhibition Sigmoid Sigmoid Sigmoid Linear Inhibition Biphasic
Vmax (pmol/min/pmol) 5.93 (5) 1.25 (19) 20.0 (1) 1.65 (8) 3.85 (3) 0.217 (5) 5.98 (5) 2.06 (8) 1.51 (19)
S50/Km (μM) 51.2 (10) 30.7 (50) 3.56 (4) 11.5 (13) 49.3 (6) 43.8 (10) 338 (8) 2.70 (24) 21.8 (35)
Hill coefficient 1.33 (8) 2.03 (11) 1.55 (9) 2.09 (8)
Ksi (μM) 137 (18) 219 (31)
Vmax2 (pmol/min/pmol) 20.6 (2)
Km2 (μM)









1217 (6)
  • Sigmoid, sigmoidal model; hyperbolic, simple hyperbolic model; inhibition, substrate inhibition model; biphasic, biphasic saturation model.

  • * Major metabolite formed in reconstituted system.