Table 2.
Effects of potent and weak cytochrome P450 (CYP) 2D6-inhibiting selective serotonin reuptake inhibitors (SSRIs) on tamoxifen pharmacokinetics
| Tamoxifen + potent CYP2D6-inhibiting SSRI | Tamoxifen + weak CYP2D6-inhibiting SSRI | Ratio of weak to potent CYP2D6-inhibiting SSRI | P valuea | |
|---|---|---|---|---|
| Tamoxifen | ||||
| C max (nM) | 369 (189–667) | 366 (177–516) | 0.97 (0.67–1.29) | 0.889 |
| C trough (nM)b | 278 (128–557) | 290 (123–375) | 0.95 (0.67–1.38) | 0.575 |
| AUC0–24 (nM·h) | 6422 (3574–12,182) | 6958 (3226–9567) | 0.98 (0.79–1.18) | 0.674 |
| ND-Tam | ||||
| C max (nM) | 528 (395–977) | 631 (365–955) | 1.09 (0.77–1.75) | 0.484 |
| C trough (nM)b | 446 (306–807) | 560 (312–704) | 0.97 (0.76–1.37) | 0.953 |
| AUC0–24 (nM·h) | 10,149 (7744–20,107) | 11,500 (7441–16,113) | 1.09 (0.75–1.27) | 0.674 |
| 4-OH-Tam | ||||
| C max (nM) | 3.46 (1.36–4.95) | 4.09 (2.42–8.25) | 1.42 (0.81–2.05) | 0.036 |
| C trough (nM)b | 2.47 (1.29–4.65) | 3.25 (1.99–6.06) | 1.40 (0.82–2.06) | 0.017 |
| AUC0–24 (nM·h) | 63.8 (27.4–98.2) | 85.8 (51.1–148) | 1.34 (0.88–1.87) | 0.017 |
| Endoxifen | ||||
| C max (nM) | 5.46 (3.86–11.1) | 23.1 (9.05–33.2) | 2.96 (1.50–7.44) | 0.012 |
| C trough (nM)b | 5.20 (3.48–10.6) | 16.3 (7.05–30.8) | 2.80 (1.02–6.33) | 0.005 |
| AUC0–24 (nM·h) | 99.2 (70.0–210) | 387 (159–637) | 2.98 (1.67–6.82) | 0.012 |
| Ratios | ||||
| Endoxifen to ND-Tam | 0.0113 (0.0065–0.014) | 0.0311 (0.018–0.057) | 3.33 (1.56–5.37) | 0.012 |
| 4-OH-Tam to tamoxifen | 0.0109 (0.0053–0.014) | 0.0149 (0.0084–0.020) | 1.51 (1.08–1.67) | 0.012 |
| Endoxifen to tamoxifen | 0.0213 (0.0057–0.029) | 0.0559 (0.034–0.10) | 2.85 (1.96–6.42) | 0.012 |
Potent CYP2D6-inhibiting SSRIs: paroxetine or fluoxetine; weak CYP2D6-inhibiting SSRIs: escitalopram (and, in one woman, citalopram)
Data are presented as median (range)
The parameters of one patient were dose corrected to 20 mg
4-OH-Tam 4-hydroxytamoxifen, AUC 0–24 area under the curve from 0 to 24 h, C max maximum concentration, C trough concentration before dosing, ND-Tam N-desmethyltamoxifen
aWilcoxon signed-rank test
b C trough data from 10 patients; the parameters of two patients were dose corrected to 20 mg