TABLE 1.
Estimated kinetic parameters for the formation of TMP primary metabolites in human liver microsomes and cDNA-expressed human P450 enzymes
Data are presented as the value ± S.E.
| Km | Vmax a,b | Clint c,d | |
|---|---|---|---|
| Section I.1 μM | |||
| Pooled HLMs | |||
| 1-NO-TMP | 1050 ± 120 | 69 ± 6 | 0.07 |
| 3-NO-TMP | 690 ± 76 | 5 ± 0.3 | 0.007 |
| 3′-desmethyl-TMP | 647 ± 55 | 453 ± 25 | 0.70 |
| 4′-desmethyl-TMP | 482 ± 42 | 146 ± 7 | 0.30 |
| Cα-OH-TMP | 2180 ± 400 | 108 ± 17 | 0.05 |
| Cα-NAC-TMP | 1310 ± 160 | 18 ± 2 | 0.01 |
| CYP2C9 | |||
| 1-NO-TMP | 531 ± 264 | 23.3 ± 6.87 | 0.044 |
| 3-NO-TMP | 428 ± 253 | 5.97 ± 1.95 | 0.014 |
| 3′-desmethyl-TMP | 1330 ± 400 | 2030 ± 470 | 1.53 |
| 4′-desmethyl-TMP | I.D. | I.D. | I.D. |
| Cα-OH-TMP | I.D. | I.D. | I.D. |
| Cα-NAC-TMP | I.D. | I.D. | I.D. |
| CYP3A4 | |||
| 1-NO-TMP | 971 ± 188 | 1320 ± 190 | 1.36 |
| 3-NO-TMP | N.D. | N.D. | N.D. |
| 3′-desmethyl-TMP | 1470 ± 510 | 2060 ± 571 | 1.40 |
| 4′-desmethyl-TMP | 1040 ± 231 | 1430 ± 240 | 1.38 |
| Cα-OH-TMP | 754 ± 122 | 1020 ± 110 | 1.35 |
| Cα-NAC-TMP | 784 ± 143 | 137 ± 18 | 0.17 |
CLint, intrinsic clearance; I.D., insufficient data to determine kinetic parameters; N.D., metabolite not detected.
a
Values are pmol/mg protein/minute for pooled HLMs.
b
Values are pmol/nmol P450/minute for heterologously expressed enzymes.
c
Values are µl/mg protein/minute for pooled HLMs.
d
Values are µl/nmol P450/minute for heterologously expressed enzymes.