Table 2.
Effects of CYP2D6 polymorphisms on median (range) plasma concentrations of analytes and plasma metabolic ratios (n = 111)
| Parameters | Genotypes | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| *1/*1 | *1/*5 | *1/*10 | *10/*10 | *5/*10 | *1/*41+*41/*41 | |||||||
| (n = 13) | (n = 9) | (n = 31) | (n = 40) | (n = 12) | (n = 6) | |||||||
| Analytes | ||||||||||||
| Tamoxifen | 161.22 | (50.06–369.89) | 216.07 | (93.56–325.56) | 194.88 | (51.80–421.16) | 217.19 | (84.27–599.91) | 169.91 | (39.26–452.29) | 166.42 | (147.72–578.17) |
| NDM | 174.59 | (40.82–448.65) | 261.07 | (206.94–464.25) | 279.43 | (115.41–502.13) | 374.41 | (84.77–802.98) | 330.67 | (78.46–757.13) | 286.30 | (159.67–511.20) |
| 4-OHT | 2.49 | (0.97–3.36) | 1.58 | (1.25–3.25) | 1.92 | (0.86–4.51) | 1.76 | (0.72–3.82) | 1.87 | (0.47–3.17) | 2.55 | (0.75–5.02) |
| Endoxifen | 19.55 | (4.18–39.47) | 14.51 | (10.73–26.04) | 19.74 | (7.26–33.24) | 8.03 | (1.74–34.68) | 7.46 | (1.79–13.77) | 16.93 | (6.37–33.99) |
| Plasma metabolic ratios (MRs) | ||||||||||||
| MREND-NDM | 10.11 | (5.63–14.86) | 5.29 | (4.48–8.00) | 6.62 | (1.65–11.65) | 2.31 | (0.92–27.81) | 2.15 | (1.06–3.30) | 6.21 | (1.94–11.85) |
| MR4-OHT-TAM | 1.34 | (0.74–1.93) | 1.04 | (0.62–1.72) | 1.08 | (0.50–2.26) | 0.83 | (0.19–1.78) | 0.94 | (0.46–1.80) | 1.00 | (0.51–2.35) |
| Total metabolic ratios (TMRs) | ||||||||||||
| TMRNDM | 5.03 | (2.94–7.45) | 3.30 | (2.61–4.56) | 3.91 | (0.98–7.24) | 1.50 | (0.51–10.69) | 1.41 | (0.65–2.21) | 3.27 | (1.35–7.37) |
| TMR4-OHT | 11.05 | (6.09–14.73) | 8.49 | (5.26–11.77) | 9.18 | (2.39–18.70) | 4.16 | (1.14–17.05) | 4.29 | (1.71–7.85) | 6.59 | (3.65–19.04) |
| Pairwise P values | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| *1/*1 vs. *1/*5 | *1/*1 vs. *1/*10 | *1/*1 vs. *10/*10 | *1/*10 vs. *10/*10 | *1/*1 vs. *5/*10 | *1/*5 vs. *5/*10 | *1/*10 vs. *5/*10 | *10/*10 vs. *5/*10 | *1/*1 vs. *1/*41+*41/*41 | |
| Analytes | |||||||||
| Tamoxifen | 0.404 | 0.177 | 0.079 | 0.578 | 0.957 | 0.477 | 0.316 | 0.171 | 0.430 |
| NDM | 0.077 | 0.006 | 0.001 | 0.011 | 0.057 | 0.434 | 0.685 | 0.409 | 0.136 |
| 4-OHT | 0.616 | 0.709 | 0.176 | 0.041 | 0.174 | 0.434 | 0.136 | 0.745 | 0.759 |
| Endoxifen | 0.243 | 0.827 | <0.001 | <0.001 | <0.001 | 0.001 | <0.001 | 0.232 | 0.792 |
| Plasma metabolic ratios (MRs) | |||||||||
| MREND-NDM | 0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.587 | 0.054 |
| MR4-OHT-TAM | 0.141 | 0.146 | <0.001 | 0.006 | 0.022 | 0.286 | 0.267 | 0.228 | 0.219 |
| Total metabolic ratios (TMRs) | |||||||||
| TMRNDM | 0.001 | 0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.811 | 0.035 |
| TMR4-OHT | 0.030 | 0.108 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.905 | 0.054 |