N-Demethylation of tamoxifen by recombinant P450 forms and liver microsomes
| Enzyme Preparation | N-Desmethytamoxifen Produced | |
|---|---|---|
| pmol/40 min/0.2 nmol P4501-a | nmol/120 min/0.2nmol P4501-b | |
| 1A1 | 276 ± 11 | 20.1 ± 3.0 |
| 1A2 | 356 ± 55 | 14.7 ± 1.4 |
| 1B1 (RAVN) | <0.51-c | 17.5 ± 2.4 |
| 1B1 (RALN) | <0.5 | 18.9 ± 0.6 |
| 1B1 (GSVN) | <0.5 | 12.3 ± 0.9 |
| 1B1 (GSLN) | <0.5 | 13.0 ± 1.3 |
| 2A6 | <0.5 | <1 |
| 2B6 | <0.5 | <1 |
| 2C9 | <0.5 | 7.2 ± 0.1 |
| 2C19 | <0.5 | 11.5 ± 1.0 |
| 2D6 | 468 ± 28 | 63.3 ± 2.0 |
| 3A4 | 111 ± 7 | 16.6 ± 0.3 |
| 3A5 | <0.5 | 22.9 ± 0.5 |
| HL24 | 109 ± 24 | N.D. |
| HL25 | 22 ± 10 | N.D. |
| HL27 | N.D. | 16.3 ± 2.2 |
| HL32 | 60 ± 22 | N.D. |
N.D., not determined.
↵1-a Incubations were carried out with 18 μM tamoxifen for 40 min using a P450 concentration of 0.2 μM. Data are the means of three determinations, corrected for apparent N-desmethyl formation in NADPH-deficient controls. Errors represent the sum of the standard errors for complete and NADPH-deficient controls.
↵1-b Incubations were carried out with 250 μM tamoxifen for 120 min. Data are the means of three determinations, corrected for apparentN-desmethyl formation in time = 0 controls. Errors represent the sum of the standard errors for complete and time = 0 controls.
↵1-c Apparent metabolite formation was not significantly higher (p > 0.01; Student's t test) to that in P450-deficient (hNPR) controls.