Table 5.
Associations between polymorphisms and AUC0–48 of gefitinib or O-desmethyl gefitinib
| Polymorphism | Genotype | N | Gefitinib AUC0–48 (µM h)a | Pb | O-desmethyl gefitinib AUC0–48 (µM h)a | Pb |
|---|---|---|---|---|---|---|
| CYP3A5*3 | *1/*1 | 1 | 12.1 | NAc | 1.94 | NAc |
| *1/*3 | 6 | 8.62 ± 3.5 | 12.9 ± 12 | |||
| *3/*3 | 11 | 9.73 ± 3.6 | 10.0 ± 16 | |||
| CYP2D6*5 and *10 | *1/*1 | 4 | 5.52 ± 0.61 | 0.00580 | 28.2 ± 23 | 0.0179 |
| *1/*5 or *1/*10 | 9 | 9.53 ± 3.0 | 6.81 ± 4.8 | |||
| 5/*10 or *10/*10 | 5 | 12.6 ± 2.2 | 3.23 ± 2.2 | |||
| ABCG2421C > A | C/C | 8 | 8.49 ± 3.5 | 0.0692 | 16.5 ± 20 | 0.459 |
| C/A | 7 | 8.69 ± 2.6 | 5.14 ± 3.7 | |||
| A/A | 3 | 14.0 ± 1.7 | 7.43 ± 7.5 | |||
| ABCB11236C > T | C/C | 4 | 12.8 ± 2.6 | 0.0724 | 7.36 ± 5.9 | 0.670 |
| C/T | 11 | 7.99 ± 2.9 | 13.4 ± 18 | |||
| T/T | 3 | 10.6 ± 3.7 | 4.57 ± 1.6 | |||
| ABCB12677G > T/A | G/G | 1 | 15.3 | NAc | 4.36 | NAc |
| G/T | 7 | 8.59 ± 3.9 | 20 ± 20 | |||
| G/A | 1 | 7.55 | 6.79 | |||
| T/T | 6 | 9.33 ± 2.8 | 20 ± 20 | |||
| T/A | 3 | 10.6 ± 3.7 | 4.57 ± 1.6 | |||
| ABCB1 3435C > T | C/C | 1 | 12.2 | NAc | 0.00 | NAc |
| C/T | 7 | 9.42 ± 4.2 | 20.0 ± 20 | |||
| T/T | 10 | 9.27 ± 3.2 | 5.03 ± 2.9 | |||
| ABCB1 diplotype | Any/Any | 6 | 11.8 ± 2.9 | 0.0492 | 6.04 ± 5.4 | 0.640 |
| TTT/Any | 12 | 8.33 ± 3.2 | 12.8 ± 17 | |||
| OATP1B1388A > G | A/A | 3 | 8.89 ± 3.1 | 0.474 | 5.10 ± 3 | 0.319 |
| A/G | 7 | 10.8 ± 2.9 | 11.2 ± 20 | |||
| G/G | 8 | 8.55 ± 4.0 | 12.1 ± 11 | |||
| OATP1B1521T > C | T/T | 13 | 9.88 ± 3.7 | NAc | 8.87 ± 9.3 | NAc |
| T/C | 4 | 8.7 ± 3.3 | 17 ± 27 | |||
| C/C | 1 | 7.55 | 6.79 | |||
| OATP1B1diplotype | *1a/*1a, *1a/*1b, or *1b/*1b | 13 | 9.88 ± 3.7 | NAc | 8.87 ± 9.3 | NAc |
| *1a/*15 or *1b/*15 | 4 | 8.70 ± 3.3 | 17.0 ± 27 | |||
| 15/*15 | 1 | 7.55 | 6.79 |
N = 18
AUC area under the plasma concentration–time curve from time 0 to 48 h
aMean ± SD
bWilcoxon or Kruskal–Wallis test
cNot analyzed because of the small number of patients in a genotype (N < 3)