Table 6.
PD parameters of CYP2C19 EMs by H+/K+-ATPase genotype after single intravenous administration of dexlansoprazole 30 mg (Mean ± SD).
| Parameter | Genotype | 0–24 h | 0–4 h | 14–24 h |
|---|---|---|---|---|
| Median (pH) | WT (n = 6) | 5.8 ± 1.4 | 6.9 ± 0.5 | 4.3 ± 1.7 |
| Het (n = 8) | 4.9 ± 2.1 | 4.5 ± 2.8 | 3.5 ± 2.2 | |
| Hom (n = 7) | 7.5 ± 0.4 | 7.8 ± 0.1 | 6.3 ± 1.3 | |
| ΔMedian (pH) | WT (n = 6) | 3.2 ± 1.0 | 4.5 ± 0.7b | 2.3 ± 1.7 |
| Het (n = 8) | 2.9 ± 1.6 | 1.9 ± 1.0a,c | 0.5 ± 0.5c | |
| Hom (n = 7) | 5.4 ± 0.3 | 5.9 ± 0.4b | 4.2 ± 0.8b | |
| Mean (pH) | WT (n = 6) | 5.6 ± 1.1 | 6.1 ± 0.5 | 4.8 ± 1.8 |
| Het (n = 8) | 5.1 ± 1.7 | 4.7 ± 2.4 | 4.1 ± 2.1 | |
| Hom (n = 7) | 6.8 ± 0.2 | 6.6 ± 0.5 | 6.2 ± 0.4 | |
| ΔMean (pH) | WT (n = 6) | 2.4 ± 0.8c | 3.4 ± 0.7 | 1.6 ± 0.9c |
| Het (n = 8) | 2.3 ± 0.6c | 2.2 ± 0.8c | 1.2 ± 0.4c | |
| Hom (n = 7) | 4.3 ± 0.4a,b | 4.3 ± 0.4b | 3.7 ± 0.5a,b | |
| TpH≥3(%) | WT (n = 6) | 79.8 ± 16.2 | 80.8 ± 8.4 | 62.4 ± 35.6 |
| Het (n = 8) | 70.1 ± 26.3 | 63.7 ± 35.7 | 53.0 ± 41.0 | |
| Hom (n = 7) | 95.1 ± 1.1 | 78.7 ± 10.0 | 96.8 ± 1.2 | |
| ΔTpH≥3 (%) | WT (n = 6) | 35.3 ± 10.3c | 51.7 ± 34.6 | 38.5 ± 26.5c |
| Het (n = 8) | 40.8 ± 11.1c | 36.4 ± 20.1 | 31.5 ± 13.0c | |
| Hom (n = 7) | 77.4 ± 6.3a,b | 62.5 ± 11.6 | 83.1 ± 5.9a,b | |
| TpH≥4(%) | WT (n = 6) | 73.1 ± 20.0 | 76.4 ± 9.4 | 52.1 ± 41.3 |
| Het (n = 8) | 62.9 ± 33.1 | 56.9 ± 39.3c | 44.6 ± 48.0 | |
| Hom (n = 7) | 87.9 ± 4.7 | 77.1 ± 11.6b | 80.4 ± 6.2 | |
| ΔTpH≥4 (%) | WT (n = 6) | 41.0 ± 16.6c | 58.6 ± 15.0 | 29.5 ± 29.9 |
| Het (n = 8) | 41.4 ± 17.3c | 35.0 ± 11.7 | 25.1 ± 16.9 | |
| Hom (n = 7) | 78.0 ± 1.5a,b | 67.2 ± 2.4 | 72.4 ± 1.5 | |
| TpH≥6(%) | WT (n = 6) | 53.5 ± 23.6 | 66.9 ± 14.8 | 34.4 ± 28.0 |
| Het (n = 8) | 48.0 ± 32.5 | 39.4 ± 48.2 | 30.2 ± 32.6 | |
| Hom (n = 7) | 73.4 ± 3.7 | 75.5 ± 12.2 | 51.5 ± 10.9 | |
| ΔTpH≥6 (%) | WT (n = 6) | 43.2 ± 18.2 | 60.9 ± 12.6 | 14.1 ± 12.6c |
| Het (n = 8) | 37.3 ± 19.1 | 33.8 ± 39.0 | 11.6 ± 2.9c | |
| Hom (n = 7) | 68.7 ± 7.9 | 70.1 ± 4.5 | 45.8 ± 17.4a,b | |
|
(pH·h) |
WT (n = 6) | 8, 178 ± 1, 587 | 1, 462 ± 111 | 2, 900 ± 1, 050 |
| Het (n = 8) | 7, 409 ± 2, 391 | 1, 147 ± 577 | 2, 505 ± 1, 248 | |
| Hom (n = 7) | 9, 806 ± 345 | 1, 588 ± 124 | 3, 697 ± 221 | |
|
(pH·h) |
WT (n = 6) | 3, 372 ± 1, 064c | 817 ± 157 | 968 ± 553c |
| Het (n = 8) | 3, 317 ± 850c | 531 ± 194c | 755 ± 198c | |
| Hom (n = 7) | 6, 157 ± 629a,b | 1, 024 ± 83b | 2, 168 ± 270a,b |
a
P < 0.05 vs. WT;
b
P < 0.05 vs. hetrozygote;
c
P < 0.05 vs. homozygote. PD, pharmacodynamic; EM, extensive metabolizer; WT, wildtype; het, heterozygote; hom, homozygote; TpH≥3(%), percentage time of pH ≥ 3; TpH≥4 (%), percentage time of pH ≥ 4; TpH≥6 (%), percent time of pH ≥ 6; , area under pH-time curve.