Table 2.
Pharmacokinetic parameters for pantoprazole, rabeprazole, and omeprazole administered under fasting and fed conditions, considering only CYP2C19*1/*1 subjects. Data are expressed as mean ± standard deviation. *p ≤ 0.05 vs. men
| n | AUC0-∞ (ng·h/ml) | Cmax (ng/ml) | Tmax (h) | t1/2 (h) | Vd/F (l/kg) | Cl/F (L/h·kg) | Ke | |
|---|---|---|---|---|---|---|---|---|
| Pantoprazole (n = 28) | ||||||||
| Fast | 14 | 6085.3 ± 2922.6 | 2539.7 ± 836.3 | 3.0 ± 0.7 | 1.2 ± 0.4 | 0.18 ± 0.03 | 0.12 ± 0.05 | 0.64 ± 0.19 |
| Men | 8 | 4780.9 ± 2471.8 | 2019.8 ± 492.8 | 3.0 ± 0.7 | 1.3 ± 0.5 | 0.20 ± 0.02 | 0.14 ± 0.06 | 0.64 ± 0.23 |
| Women | 6 | 7824.6 ± 2702.2 | 3233.0 ± 685.0 | 2.9 ± 0.8 | 1.1 ± 0.2 | 0.16 ± 0.04 | 0.11 ± 0.04 | 0.63 ± 0.12 |
| Fed | 14 | 4689.0 ± 2303.3 | 2660.7 ± 531.2 | 5.7 ± 1.2 | 1.2 ± 0.5 | 0.24 ± 0.05 | 0.16 ± 0.07 | 0.67 ± 0.20 |
| Men | 8 | 4520.4 ± 2518.4 | 2564.3 ± 581.1 | 5.3 ± 1.1 | 1.2 ± 0.6 | 0.23 ± 0.03 | 0.15 ± 0.07 | 0.67 ± 0.25 |
| Women | 6 | 4913.8 ± 2192.7 | 2789.3 ± 475.5 | 6.2 ± 1.1 | 1.1 ± 0.3 | 0.25 ± 0.06 | 0.17 ± 0.08 | 0.68 ± 0.14 |
|
Fed vs. Fast ratio; 90% CI; p value |
74.8; 55.8–100.1 p = 0.1010 |
103.5; 91.3–117.2 p = 0.6431 |
192.2; 166.5–221.9 p = 0.001 |
95.6; 76.7–119.0 p = 0.7262 |
127.5; 113.2–143.6 p = 0.0018 |
129.1; 96.7–172.3 p = 0.1439 |
104.6; 84.0–130.3 p = 0.7262 |
|
| Rabeprazole (n = 23) | ||||||||
| Fast | 14 | 901.2 ± 234.6 | 536.3 ± 138.2 | 3.9 ± 0.8 | 1.3 ± 0.6 | 0.60 ± 0.11 | 0.37 ± 0.09 | 0.63 ± 0.20 |
| Men | 7 | 870.2 ± 295.6 | 512.2 ± 146.8 | 3.9 ± 1.0 | 1.5 ± 0.7 | 0.59 ± 0.10 | 0.33 ± 0.10 | 0.57 ± 0.25 |
| Women | 7 | 932.2 ± 172.0 | 560.4 ± 135.8 | 3.8 ± 0.7 | 1.1 ± 0.2 | 0.61 ± 0.12 | 0.41 ± 0.07 | 0.68 ± 0.13 |
| Fed | 9 | 968.9 ± 387.5 | 606.3 ± 206.8 | 9.1 ± 3.3 | 2.0 ± 0.9 | 0.92 ± 0.34 | 0.38 ± 0.18 | 0.45 ± 0.23 |
| Men | 4 | 999.7 ± 322.7 | 572.2 ± 215.1 | 10.3 ± 5.1 | 2.5 ± 0.7 | 1.02 ± 0.39 | 0.30 ± 0.11 | 0.30 ± 0.11 |
| Women | 5 | 944.2 ± 469.6* | 633.6 ± 220.7 | 8.2 ± 0.6 | 1.5 ± 0.9* | 0.85 ± 0.32 | 0.45 ± 0.20* | 0.57 ± 0.25* |
| Fed vs. Fast |
104.5; 82.7–131.9 p = 0.7488 |
111.7; 89.5–139.2 p = 0.3987 |
228.8; 187.0–278.9 p = 0.0001 |
152.0; 113.4–203.7 p = 0.023 |
147.6; 121.6–179.3 p = 0.0025 |
94.7; 75.1–119.5 p = 0.6913 |
65.8; 49.1–88.2 p = 0.023 |
|
| Omeprazole (n = 36) | ||||||||
| Fast | 15 | 1709.0 ± 1299.6 | 859.5 ± 394.9 | 1.8 ± 0.6 | 1.0 ± 0.4 | 0.69 ± 0.38 | 0.57 ± 0.39 | 0.81 ± 0.23 |
| Men | 8 | 1474.9 ± 1403.1 | 654.1 ± 305.6 | 2.0 ± 0.7 | 0.9 ± 0.4 | 0.68 ± 0.46 | 0.62 ± 0.44 | 0.82 ± 0.25 |
| Women | 7 | 1976.5 ± 1219.8 | 1094.3 ± 366.6 | 1.5 ± 0.3 | 1.0 ± 0.3 | 0.69 ± 0.46 | 0.53 ± 0.36 | 0.79 ± 0.23 |
| Fed | 16# | 1523.3 ± 1290.5 | 604.4 ± 362.6 | 4.7 ± 1.0 | 1.0 ± 0.4 | 0.77 ± 0.43 | 0.62 ± 0.41 | 0.80 ± 0.36 |
| Men | 10 | 1409.7 ± 1162.1 | 582.8 ± 419.1 | 4.3 ± 1.0 | 1.0 ± 0.4 | 0.73 ± 0.38 | 0.63 ± 0.49 | 0.84 ± 0.39 |
| Women | 6 | 1712.7 ± 1250.2 | 640.4 ± 275.1 | 5.4 ± 0.4 | 1.1 ± 0.4 | 0.84 ± 0.54 | 0.57 ± 0.29 | 0.72 ± 0.32 |
|
Fed vs. Fast ratio; 90% CI; p value |
88.5; 82.4–95.1 p = 0.0101 |
64.3; 52.5–78.7 p = 0.0019 |
278.3; 227.7–340.1 p = 0.0001 |
104.8; 87.7–125.3 p = 0.6457 |
118.9; 93.3–151.5 p = 0.2271 |
115.3; 105.3–126.2 p = 0.0159 |
95.4; 79.8–114.0 p = 0.6457 |
|
#15 of the subjects participated in both fast and fed omeprazole clinical trials