Table 2.
Tamoxifen pharmacokinetics.
| 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 |
|---|---|---|---|---|---|---|---|
| Tamoxifen | |||||||
| AUC0–24h | 5951 (20) | 5460 (24) | 5171 (23) | −8.0% (−14.1 to −1.4) |
0.02 | −12.8% (−19.2 to −5.9) |
<0.01 |
| Ctrough | 213 (27) | 198 (28) | 187 (24) | −7.1% (−17.1 to +4.0) |
0.25 | −12.2% (−21.5 to −1.8) |
0.02 |
| Cmax | 356 (16) | 324 (21) | 313 (22) | −8.4% (−16.4 to +0.5) |
0.07 | −11.1% (−18.1 to −3.6) |
<0.01 |
| Tmax | 2.4 (1.9 to 3.1) |
2.4 (1.9 to 3.0) |
2.7 (1.9 to 3.8) |
0.74 | 0.34 | ||
| Endoxifen | |||||||
| AUC0–24h | 597 (59) | 556 (52) | 518 (54) | −7.7 % (−15.4 to +0.7) |
0.07 | −12.4% (−21.9 to −1.9) |
0.02 |
| Ctrough | 25 (60) | 23 (53) | 21 (55) | −5.6 % (−15.6 to +5.5) |
0.43 | −12.4% (−20.9 to −3.0) |
0.01 |
| Cmax | 31 (56) | 28 (50) | 27 (51) | −7.1% (−16.3 to +3.2) |
0.20 | −9.8% (−20.1 to +1.8) |
0.10 |
| Tmax | 2.0 (1.3 to 3.0) |
1.7 (1.2 to 2.6) |
1.8 (1.1 to 3.1) |
0.88 | 0.62 | ||
| 4-hydroxy-tamoxifen | |||||||
| AUC0–24h | 113 (31) | 106 (24) | 103 (28) | −6.3 % (−11.6 to −0.73) |
0.03 | −8.2% (−17.0 to +1.6) |
0.11 |
| Ctrough | 4.4 (34) | 4.2 (26) | 4.1 (28) | −4.3 % (−12.3 to +4.4) |
0.45 | −7.3 (−17.6 to +4.3) |
0.26 |
| Cmax | 6.0 (32) | 5.4 (26) | 5.4 (31) | −10.0% (−16.8 to −2.6) |
<0.01 | −8.8% (−20.0 to +4.0) |
0.20 |
| Tmax | 2.7 (1.9 to 3.9) |
2.4 (1.8 to 3.3) |
2.8 (2.0 to 3.8) |
0.42 | 0.37 | ||
| N -desmethyl-tamoxifen | |||||||
| AUC0–24h | 11596 (21) | 10766 (24) | 10084 (31) | −7.0% (−13.1 to −0.6) |
0.03 | −12.4% (−22.3 to −1.3) |
0.03 |
| Ctrough | 463 (28) | 430 (29) | 411 (32) | −7.2% (−15.0 to +1.2) |
0.10 | −10.9% (−21.6 to +1.3) |
0.08 |
| Cmax | 602 (21) | 556 (24) | 540 (32) | −7.2% (−14.9 to +1.1) |
0.09 | −9.7% (−20.2 to +2.3) |
0.12 |
| Tmax | 2.6 (1.8 to 3.7) |
1.7 (1.2 to 2.4) |
2.1 (1.4 to 3.2) |
0.24 | 0.88 | ||
Abbreviations: PK = pharmacokinetics; CI = Confidence Interval; AUC0–24h= area under the curve, timepoint 0 h to 24 h (expressed as geomean nM·h/mL (CV%)); Ctrough= minimum concentration (expressed as geomean nM/mL (CV%)); Cmax= maximum concentration (expressed as geomean nM/mL (CV%)); Tmax= time until maximum concentration (expressed as median h (IQR)); CV% = coefficient of variation; IQR = interquartile range.