Table 2.
Pharmacokinetic parameters of four CYP substrates in sham rats and hemorrhagic shock model rats at 24 h after resuscitation with PRBC and Hb-V.
| Sham | PRBC | Hb-V | |
|---|---|---|---|
| Caffeine (CYP 1A2) | |||
| t1/2 (hr) | 1.5 ± 0.2 | 2.1 ± 0.2# | 4.7 ± 1.7∗∗ |
| AUCinf (μg × hr/mL) | 14.1 ± 1.0 | 20.0 ± 2.1# | 37.0 ± 11.6∗∗ |
| MRT (hr) | 2.1 ± 0.3 | 3.0 ± 0.4# | 6.7 ± 2.4∗∗ |
| CLtot (mL/hr) | 355.8 ± 24.6 | 252.2 ± 28.4∗∗## | 146.2 ± 48.9∗∗ |
| Vd (mL) | 734.5 ± 68.5 | 756.4 ± 22.9# | 902.0 ± 70.0∗∗ |
| Tolbutamide (CYP 2C11) | |||
| t1/2 (hr) | 4.4 ± 0.2 | 5.0 ± 0.7# | 6.0 ± 0.3∗∗ |
| AUCinf (μg × hr/mL) | 173.8 ± 4.3 | 195.7 ± 30.8 | 184.3 ± 21.7 |
| MRT (hr) | 6.3 ± 0.2 | 7.2 ± 0.9# | 8.7 ± 0.5∗∗ |
| CLtot (mL/hr) | 14.4 ± 0.4 | 13 ± 2.2 | 13.7 ± 1.7 |
| Vd (mL) | 90.7 ± 5.1 | 92.9 ± 5.4## | 118.5 ± 9.1∗∗ |
| Chlorzoxazone (CYP 2E1) | |||
| t1/2 (hr) | 1.0 ± 0.2 | 1.3 ± 0.2# | 2.0 ± 0.3∗∗ |
| AUCinf (μg × hr/mL) | 28.5 ± 1.8 | 36.5 ± 6.2 | 41.4 ± 4.0∗∗ |
| MRT (hr) | 1.5 ± 0.3 | 1.9 ± 0.3# | 2.8 ± 0.5∗∗ |
| CLtot (mL/hr) | 175.8 ± 11.4 | 140.2 ± 23.9∗ | 121.5 ± 12.1∗∗ |
| Vd (mL) | 258 ± 32.9 | 255.3 ± 8.5## | 341.6 ± 37.6∗∗ |
| Midazolam (CYP 3A2) | |||
| t1/2 (hr) | 0.19 ± 0.04 | 0.18 ± 0.02 | 0.23 ± 0.03 |
| AUCinf (μg × hr/mL) | 1.0 ± 0.1 | 1.3 ± 0.1 | 1.6 ± 0.3∗ |
| MRT (hr) | 0.25 ± 0.04 | 0.23 ± 0.03 | 0.28 ± 0.05 |
| CLtot (L/hr) | 7.7 ± 0.4 | 5.8 ± 0.5∗ | 4.9 ± 1.2∗∗ |
| Vd (L) | 1.9 ± 0.4 | 1.3 ± 0.1∗ | 1.4 ± 0.2∗ |
t1/2, the half-life; AUCinf, area under the concentration-time curve; MRT, mean residence time; CLtot, clearance; Vd, distribution volume.
The values are means ± SD; n = 4 each group.
∗p < 0.05, ∗∗p < 0.01 vs. sham group, #p < 0.05, ##p < 0.01 vs. Hb-V group.