TABLE 2

Steady-state kinetic analysis: CPA, R-IFA, and S-IFA metabolism by cDNA-expressed P450s 2B1, 2B6, and 3A4

Data shown are mean ± S.D. values based on n = 3 independent determinations.


P450

Prodrug

4-Hydroxylation

N-Dechloroethylation
Km
Vmax
Km
Vmax
mM mol/min/mol P450 mM mol/min/mol P450
2B1 CPA 0.40 ± 0.06 73.5 ± 7.5 0.55 ± 0.13 3.0 ± 0.7
R-IFA 0.54 ± 0.10 19.0 ± 1.5 0.70 ± 0.22 43.6 ± 14.5
S-IFA 0.56 ± 0.06 32.2 ± 1.4 0.69 ± 0.04 27.2 ± 6.4
2B6 CPA 1.33 ± 0.04 123.2 ± 5.5 N.D. 0
R-IFA 2.24 ± 1.15 1.98 ± 0.6 1.42 ± 0.38 62.3 ± 3.8
S-IFA 1.27 ± 0.24 17.1 ± 2.8 1.24 ± 0.20 58.3 ± 4.2
3A4 CPA 1.13 ± 0.22 31.9 ± 4.9 1.61 ± 0.22 94.2 ± 9.1
R-IFA 0.98 ± 1.14 63.7 ± 7.2 1.10 ± 0.27 26.0 ± 5.7

S-IFA
0.99 ± 0.24
25.0 ± 2.4
1.50 ± 0.30
125 ± 23
  • N.D., not determined due to low activity.