Pharmacokinetic
Parameters |
Mouse |
Rat |
Dog |
Monkey |
Microminipig |
| i.v. |
p.o. |
i.v. |
p.o. |
i.v. |
p.o. |
i.v. |
p.o. |
i.v. |
p.o. |
| Omeprazole |
|
|
|
|
|
|
|
|
|
|
| Cmax (ng/ml) |
|
1.27 |
|
7.61 ± 5.98 |
|
102 ± 21 |
|
53.8 ± 12.8 |
|
82.1 ± 6.9 |
| Tmax (h) |
|
0.250 |
|
0.250 ± 0.00 |
|
0.250 ± 0.00 |
|
1.25 ± 0.66 |
|
0.583 ± 0.382 |
| t1/2(h) |
0.200 |
0.973 |
0.179 ± 0.007 |
N.C. |
0.741 ± 0.392 |
0.666 ± 0.238 |
0.745 ± 0.383 |
0.572 ± 0.154 |
0.951 ± 0.247 |
2.15 ± 1.81 |
| AUC0-24h (h･ng/ml) |
42.7 |
1.30 |
349 ± 110 |
6.61 ± 5.01 |
598 ± 23 |
160 ± 19 |
879 ± 96 |
111 ± 47 |
1487 ± 648 |
255 ± 128 |
| Vd,ss(ml/kg) |
770 |
|
243 ± 87 |
|
369 ± 31 |
|
173 ± 49 |
|
144 ± 19 |
|
| CLtot (ml/h/kg) |
7754 |
|
1028 ± 395 |
|
555 ± 21 |
|
379 ± 41 |
|
268 ± 155 |
|
| BA (%) |
|
3.05 |
|
1.89 |
|
26.7 ± 2.7 |
|
12.3 ± 4.0 |
|
17.7 ± 5.27 |
| |
|
|
|
|
|
|
|
|
|
|
| 5-Hydroxyomeprazole |
|
|
|
|
|
|
|
|
|
|
| Cmax (ng/ml) |
|
6.92 |
|
10.9 ± 5.3 |
|
20.0 ± 6.6 |
|
18.5 ± 2.4 |
|
14.6 ± 1.3 |
| Tmax (h) |
|
0.250 |
|
0.250 ± 0.00 |
|
0.750 ± 0.250 |
|
1.25 ± 0.66 |
|
1.08 ± 0.80 |
| t1/2 (h) |
|
1.27 |
|
1.60 ± 0.12 |
|
0.869 ± 0.187 |
|
0.703 ± 0.192 |
|
1.57 ± 0.38 |
| AUC0-24h (h･ng/ml) |
|
5.36 |
|
12.6 ± 7.4 |
|
46.1 ± 8.3 |
|
41.3 ± 3.4 |
|
57.5 ± 22.1 |
AUC0-24h ratio of 5-hydroxyomeprazole/
omeprazole |
|
3.94 |
|
1.81 |
|
0.276 ± 0.047 |
|
0.387 ± 0.109 |
|
0.231 ± 0.070 |
|
Each data represents the mean ± S.D. of three determinations, except for data in mice and, BA and AUC0-24h of 5-hydroxyomeprazole/omeprazole in rats.
Data in mice are calculated from the average plasma concentration of the three animals. BA and AUC0-24h of 5-hydroxyomeprazole/omeprazole in rats are calculated using
the average AUC0-24h of the three animals.
i.v., intravenous; p.o., peroral; Cmax, the peak plasma concentration; Tmax, the time to reach Cmax; t1/2, terminal elimination half-life; AUC0-24h, area under the plasma concentration
vs. time curve from 0 h to 24 h; Vd,ss, volume of distribution; CLtot, total body clearance; BA, bioavailability; N.C., not calculated. |
| Table 3: Pharmacokinetic parameters of omeprazole and 5-hydroxyomeprazole in mice, rats, dogs, monkeys, and microminipigs after the intravenous and oral administrations of 5 CYP substrates such as caffeine, losartan, omeprazole, dextromethorphan, and midazolam. |
