Table 1

Comparison of enzyme kinetic parameters for CYP3A4-, CYP3A5- and CYP3A7-catalyzed metabolite formation

MetaboliteCYP3A4CYP3A5CYP3A7
Best Fit to ModelVmaxS50/Km1-an1-bBest Fit to ModelVmaxS50/Km1-an1-bBest Fit to ModelVmaxS50/Km1-an1-b
nmol/min/nmol P450 μM nmol/min/nmol P450 μM nmol/min/nmol P450 μM
1′-OH Midazolam1-150 SI355N.A.1-c MM7214N.A.1-c MM4114N.A.1-c
4-OH MidazolamMM4059N.A.1-c MM17116N.A.1-c Hill101571.9
1′-OH AlprazolamMM455N.A.1-c MM4178N.A.1-c MM0.21177N.A.1-c
4-OH Alprazolam1-150 Hill199811.4Hill4071261.8Hill3821.9
1′-OH Triazolam1-150 Hill17171.3Hill11621.9Hill0.941441.4
4-OH TriazolamMM37157N.A.1-c Hill171291.6Hill5.652811.1
N-Desmethyl diltiazemMM3144N.A.1-c Hill722241.3MM26182N.A.1-c
6β-OH TestosteroneHill111291.2MM21243N.A.1-c Hill0.96281.4
N-Desmethyl clarithromycin1-150 MM71711N.A.1-c MMN.A.1-d N.A.1-d N.A.1-c MM54991N.A.1-c
14-OH ClarithromycinMM13220N.A.1-c MMN.A.1-d N.A.1-d N.A.1-c MM2950N.A.1-c
2-OH Estradiol1-150 MM1018N.A.1-c MM0.4336N.A.1-c MM0.1318N.A.1-c
4-OH EstradiolMM1.8314N.A.1-c MM0.2127N.A.1-c MM0.0219N.A.1-c
Oxidized nifedipineHill3831.5MM1669N.A.1-c MM234N.A.1-c
7-OH-4-Trifluoro-methylcoumarinMM0.6831N.A.1-c MM0.0334N.A.1-c MM0.0230N.A.1-c
N-Desmethyl tamoxifenMM1050N.A.1-c MM624N.A.1-c MM15819N.A.1-c
  • SI, substrate inhibition equation; MM, Michaelis-Menten; Hill, Hill equation; N.A., not applicable.

  • 1-150  Major metabolite.

  • 1-a  Km orS50 values in this Table are derived from the best fit model to either Michaelis-Menten or Hill equations respectively, except for CYP3A4-mediated 1′-OH midazolam formation, which best fit a substrate inhibition kinetic model (Ki = 2438 μM).

  • 1-b  Hill coefficient, indicating the degree of sigmoidicity, for data that fits the Hill equation best.

  • 1-c  Did not fit the Hill equation.

  • 1-d  Rates of metabolite formation were not saturated up to the highest substrate concentration tested.