TABLE 3

Calculated CYP3A4 and CYP3A5 intrinsic clearance based on fitted kinetic parameters

Calculation of in vitro intrinsic clearance: hyperbolic model, CL′int = Vmax/Km; substrate inhibition model, CL′int = Vmax/Km; biphasic saturation model, CL′int = Vmax1/Km1 (high affinity, low capacity); and sigmoidal model, CL′int max = V/[S] = (Vmax/S50/n) × (n - 1)1 - 1/n


Metabolite

CYP3A4

CYP3A5

3A5/3A4 Ratio
ml/min/nmol
6β-OH TST 0.104 0.066 0.63
N-Desmethyl ERM 0.099 0.041 0.41
1′-OH MDZ 1.84 5.62 3.05
4-OH MDZ 0.16 0.14 0.88
3-OH FLZ 0.11 0.039 0.35
Desmethyl FLZ 0.015 0.003 0.20
CBZ 10,11-epoxide 0.010 0.009 0.90
3-MM 0.015 0.016* 1.07
TFN alcohol 1.72 0.763 0.44
MEGX
0.051
0.069
1.35
  • * Estimated from a regression of the “linear” velocity-substrate concentration plot.