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.