Table 3.
Effects of CYP2C19 polymorphisms on median (range) plasma concentrations (ng ml−1) and metabolic ratios of tamoxifen and its analytes (n = 165)
| Parameters | Genotypes | Pairwise P value | |||||||
|---|---|---|---|---|---|---|---|---|---|
| CYP2C19*2 | *1/*1 | *1/*2 | *2/*2 | *1/*1 vs.*1/*2 | *1/*1 vs.*2/*2 | *1/*2 vs.*2/*2 | |||
| (681G>A; rs4244285) | (n = 40) | (n = 44) | (n = 22) | ||||||
| Analytes | |||||||||
| Tamoxifen | 190.05 | (50.06–578.17) | 204.38 | (39.26–599.91) | 186.28 | (84.27–421.16) | 0.736 | 0.783 | 0.955 |
| NDM | 346.62 | (40.82–734.94) | 284.90 | (78.46–802.98) | 305.23 | (84.77–757.13) | 0.392 | 0.421 | 0.996 |
| 4-OHT | 1.78 | (0.70–5.02) | 2.10 | (0.47–5.33) | 2.23 | (0.87–4.51) | 0.305 | 0.480 | 0.749 |
| Endoxifen | 10.47 | (3.48–42.80) | 14.51 | (1.79–42.56) | 16.34 | (1.74–28.64) | 0.358 | 0.246 | 0.553 |
| Plasma metabolic ratios (MRs) | |||||||||
| MRNDM-TAM | 1.63 | (0.82–2.76) | 1.51 | (0.62–2.65) | 1.44 | (1.01–2.10) | 0.208 | 0.088 | 0.470 |
| MREND-4-OHT | 6.63 | (3.70–13.18) | 7.05 | (2.44–11.96) | 6.97 | (1.99–12.34) | 0.793 | 0.428 | 0.613 |
| Total metabolic ratios (TMRs) | |||||||||
| TMRNDM | 2.16 | (0.65–7.46) | 3.05 | (0.51–10.69) | 3.42 | (1.03–5.86) | 0.387 | 0.421 | 0.650 |
| TMR4-OHT | 5.96 | (1.71–19.50) | 7.28 | (1.14–18.00) | 7.34 | (2.04–15.33) | 0.408 | 0.438 | 0.836 |
| CYP2C19*3 | *1/*1 | *1/*3+*3/*3 | *1/*1 vs.*1/*3+*3/*3 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| (636G>A; rs4986893) | (n = 40) | (n = 8) | |||||||
| Analytes | |||||||||
| Tamoxifen | 190.05 | (50.06–578.17) | 211.17 | (164.79–364.69) | 0.138 | ||||
| NDM | 346.62 | (40.82–734.94) | 323.23 | (215.01–590.65) | 0.415 | ||||
| 4-OHT | 1.78 | (0.70–5.02) | 1.92 | (1.10–3.82) | 0.800 | ||||
| Endoxifen | 10.47 | (3.48–42.80) | 13.69 | (4.74–23.04) | 0.935 | ||||
| Plasma metabolic ratios (MRs) | |||||||||
| MRNDM-TAM | 1.63 | (0.82–2.76) | 1.53 | (1.06–1.95) | 0.328 | ||||
| MREND-4-OHT | 6.63 | (3.70–13.18) | 5.61 | (3.74–11.69) | 0.786 | ||||
| Total metabolic ratios (TMRs) | |||||||||
| TMRNDM | 2.16 | (0.65–7.46) | 1.99 | (0.75–5.52) | 0.395 | ||||
| TMR4-OHT | 5.96 | (1.71–19.50) | 4.55 | (1.83–11.74) | 0.405 | ||||
| CYP2C19*17 | *1/*1 | *1/*17 | *1/*1 vs.*1/*17 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| (-3402C>T and −806C>T; rs12248560) | (n=40) | (n=6) | |||||||
| Analytes | |||||||||
| Tamoxifen | 190.05 | (50.06–578.17) | 211.65 | (100.24–369.89) | 0.887 | ||||
| NDM | 346.62 | (40.82–734.94) | 318.49 | (159.67–403.52) | 0.404 | ||||
| 4-OHT | 1.78 | (0.70–5.02) | 2.68 | (0.96–4.84) | 0.190 | ||||
| Endoxifen | 10.47 | (3.48–42.80) | 18.35 | (6.37–31.05) | 0.416 | ||||
| Plasma metabolic ratios (MRs) | |||||||||
| MRNDM-TAM | 1.63 | (0.82–2.76) | 1.64 | (0.92–1.77) | 0.422 | ||||
| MREND-4-OHT | 6.63 | (3.70–13.18) | 6.66 | (4.50–10.06) | 0.815 | ||||
| Total metabolic ratios (TMRs) | |||||||||
| TMRNDM | 2.16 | (0.65–7.46) | 2.94 | (1.67–7.37) | 0.140 | ||||
| TMR4-OHT | 5.96 | (1.71–19.50) | 6.78 | (3.65–19.04) | 0.281 | ||||