Table 3.
Tamoxifen pharmacokinetics, based on CYP2D6 phenotype.
| PK Parameters | Tamoxifen Monotherapy (A) | Tamoxifen + Curcumin (B) | Tamoxifen + Curcumin + Piperine (C) | Relative Difference A vs B (95%CI) | p-Value | Relative Difference A vs C (95%CI) | p-Value |
|---|---|---|---|---|---|---|---|
| Intermediate Metabolizers (IM) | |||||||
| Tamoxifen AUC0–24h | 5795 (4895–6859) |
5427 (4313–6830) |
5518 (4679–6508) |
−7.2% (−18.2 to +5.4) |
0.19 | −5.3% (−13.1 to +3.1) |
0.16 * |
| Tamoxifen Ctrough | 200 (160–251) |
191 (146–249) |
199 (167–237) |
−5.9% (−20.9to +11.9) |
0.41 | −1.3% (−15.3 to 15.1) |
0.84 * |
| Endoxifen AUC0–24h | 523 (362–755) |
472 (339–656) |
477 (340–669) |
−9.4% (−21.7 to +4.8) |
0.14 | −10.3% (−23.5 to 5.3) |
0.14 |
| Endoxifen Ctrough | 21 (14–32) |
19 (13–27) |
19 (14–27) |
−10.7% (−28.2 to 11.2) |
0.24 | −8.3% (−27.2 to 15.4) |
0.38 |
| Extensive Metabolizers (EM) | |||||||
| Tamoxifen AUC0–24h | 6077 (4882–7565) |
5471 (4247–7047) |
4836 (3720–6288) |
−10.3% (−19.7 to +0.3) |
0.06 | −22.0% (−29.0 to −4.2) |
<0.01 * |
| Tamoxifen Ctrough | 218 (163–291) |
199 (148–268) |
170 (132–218) |
−9.6% (−26.4 to +11.2) |
0.27 | −24.6% (−33.9 to −14.1) |
<0.01 * |
| Endoxifen AUC0–24h | 745 (576–963) |
716 (574–893) |
596 (495–717) |
−5.7% (−19.6 to +10.7) |
0.39 | −18.4% (−36.1 to +4.3) |
0.09 |
| Endoxifen Ctrough | 30 (23–39) |
31 (25–38) |
25 (20–30) |
−0.3% (−12.8 to +13.9) |
0.96 | −17.2% (−26.1 to −7.3) |
<0.01 * |
Abbreviations: PK = pharmacokinetics; CI = Confidence Interval; AUC0–24h= Area under the curve, timepoint 0 h to 24 h (expressed as geomean nM·h/mL (95%CI)); Ctrough= minimum concentration (expressed as geomean nM/mL (95%CI)); * Interaction term reached statistical significance (p < 0.05).