Table 3 Polymorphisms and genotype clusters with significant effect on ATV pharmacokinetics
Pharmacokinetics parameters | |||||||
Genotypes | N | Cmax (ng/mL) | AUC0-t (ng/mL*h) | AUC0-∞ (ng/mL*h) | Cl/F (L/h) | T1/2 (h) | Ke |
MTHFR rs1801133 | |||||||
C/C | 14 | 60.46 ± 20.60 | 195.77 ± 91.84 | 213.25 ± 94.16 | 448.86 ± 202.58 | 12.95 ± 9.30 | 0.07 ± 0.04 |
C/T | 37 | 44.81 ± 24.32* | 152.83 ± 87.67 | 166.43 ± 86.52 | 595.20 ± 274.47 | 10.78 ± 5.84 | 0.08 ± 0.04 |
T/T | 9 | 34.89 ± 12.90** | 141.64 ± 66.29 | 151.57 ± 67.28 | 623.70 ± 287.68 | 9.94 ± 4.19 | 0.08 ± 0.03 |
C/T + T/T | 46 | 42.87 ± 22.77§ | 150.64 ± 83.37§ | 163.52 ± 82.64§ | 600.77 ± 274.06§ | 10.62 ± 5.52 | 0.08 ± 0.03 |
DRD3 rs6280 | |||||||
C/C | 17 | 39.90 ± 14.47 | 149.50 ± 59.86 | 159.43 ± 57.99 | 562.72 ± 200.54 | 8.63 ± 2.33¢ | 0.08 ± 0.02¢ |
C/T | 26 | 44.12 ± 23.77 | 143.60 ± 85.50 | 156.77 ± 86.61 | 654.34 ± 316.38 | 10.67 ± 6.65 | 0.09 ± 0.04 |
T/T | 17 | 58.41 ± 26.70# | 199.72 ± 102.65§§, # | 218.89 ± 100.70§§, # | 431.78 ± 177.83§§, # | 14.44 ± 8.15§§, # | 0.06 ± 0.03§§, # |
C/C + C/T | 43 | 42.45 ± 20.51 | 145.93 ± 75.66 | 157.83 ± 75.82 | 618.12 ± 277.41 | 9.86 ± 5.43 | 0.09 ± 0.04 |
GSTM3 rs1799735 | |||||||
*A/*A | 55 | 44.71 ± 21.36 | 158.00 ± 89.57 | 171.60 ± 90.03 | 582.27 ± 270.90 | 10.92 ± 6.24 | 0.08 ± 0.03 |
*A/*B | 5 | 71.92 ± 32.15 | 196.08 ± 33.24 | 213.93 ± 28.26¥ | 378.87 ± 46.77¥ | 13.82 ± 10.17 | 0.08 ± 0.07 |
TNF rs1800629 | |||||||
G/G | 51 | 45.54 ± 22.80 | 153.18 ± 82.16 | 167.14 ± 83.12 | 586.66 ± 266.42 | 10.59 ± 6.14 | 0.08 ± 0.04 |
G/A | 9 | 55.88 ± 26.94 | 215.85 ± 96.68€ | 230.57 ± 93.37€ | 391.55 ± 132.91€ | 14.66 ± 8.45€ | 0.06 ± 0.02€ |
MDR1 rs1045642 | |||||||
C/C | 13 | 33.43 ± 13.40 | 135.68 ± 78.72 | 150.53 ± 79.10 | 699.77 ± 376.59 | 10.87 ± 4.99 | 0.08 ± 0.04 |
C/T + T/T | 47 | 50.78 ± 24.21¤ | 168.22 ± 88.36 | 181.93 ± 88.95 | 528.14 ± 216.66 | 11.24 ± 7.00 | 0.08 ± 0.03 |
SLCO1B1 rs4149056 | |||||||
C/C + C/T | 11 | 53.92 ± 24.72 | 222.27 ± 91.48 | 241.23 ± 92.98 | 390.51 ± 195.46 | 12.42 ± 8.59 | 0.07 ± 0.03 |
T/T | 49 | 45.41 ± 23.01 | 147.45 ± 80.40≠ | 160.29 ± 79.55≠ | 604.57 ± 264.87≠ | 10.88 ± 6.12 | 0.08 ± 0.04 |
P-values of genotype combinations on ATV pharmacokinetics | |||||||
Clusters | Cmax | AUC0-t | AUC0-∞ | Cl/F | T1/2 | Ke | |
A vs. B | 0.163 | 0.060 | 0.041£ | 0.041£ | 0.519 | 0.519 | |
B vs. C | 0.007£ | 4 × 10−4£ | 0.001£ | 0.001£ | 0.177 | 0.177 | |
A vs. C | 0.016£ | 0.011£ | 0.011£ | 0.011£ | 0.181 | 0.181 | |
C vs. A + B | 0.001£ | 9.1 × 10−5£ | 1.31 × 10−4£ | 9.5 × 10−5£ | 0.112 | 0.399 | |
D vs. E | 0.187 | 0.060 | 0.041£ | 0.002£ | 0.610 | 0.486 | |
E vs. F | 2.3 × 10−4£ | 0.001£ | 0.001£ | 0.004£ | 0.241 | 0.260 | |
D vs. F | 1 × 10−3£ | 0.014£ | 0.011£ | 6 × 10−6£ | 0.230 | 0.177 | |
F vs. D + E | 5.3 × 10−5£ | 3.61 × 10−4£ | 4.22 × 10−4£ | 1.35 × 10−4£ | 0.115 | 0.176 | |