Treatment | Cmaxb | AUC0→∞c | Extrap | t1/2 | CL/F | Vz/F | |
---|---|---|---|---|---|---|---|
% | h | l/h | liters | ||||
Substrate | |||||||
MDZ | Control | 173.0 ± 53.7 | 321.5 ± 51.0 | 21.93 | 1.36 ± 0.27 | 0.288 ± 0.051 | 0.558 ± 0.113 |
PCNa | 16.06 ± 13.4* | 13.1 ± 3.7 | 1.24 | 0.52a | 3.8 × 10−5 | 1.8 × 103 | |
3-MC | 56.90 ± 11.8* | 74.6 ± 32.5* | 13.12 | 0.867 ± 0.274** | 1.26 ± 0.45*** | 1.51 ± 0.63** | |
PHE | Control | 425.8 ± 256.9 | 154.4 ± 93.3 | 18.37 | 0.466 ± 0.137 | 3.74 ± 1.57 | 2.52 ± 1.47 |
PCN | 550.0 ± 386.2 | 150.1 ± 68.4 | 10.64 | 0.155 ± 0.044*** | 3.24 ± 1.59 | 0.761 ± 0.589 | |
3-MCa | 72.0 | 4.6 | 0.01 | ND | ND | ND | |
DXM | Control | 237.2 ± 88.2 | 646.9 ± 137.6 | 25.44 | 1.39 ± 0.36 | 39.6 ± 12.3 | 122 ± 85 |
PCN | 143.4 ± 60.6 | 213.0 ± 36.4*** | 30.84 | 1.09 ± 0.47 | 158 ± 57 | 220 ± 53 | |
3-MC | 154.5 ± 97.9 | 42.3 ± 82.5*** | 27.14 | 1.20 ± 0.81 | 169 ± 121 | 206 ± 70 | |
DIC | Control | 49.15 ± 13.99 | 45.23 ± 14.39 | 1.78 | 0.418 ± 0.043 | 1.37 ± 0.97 | 0.797 ± 0.504 |
PCN | 6.592 ± 2.613* | 7.23 ± 2.81* | 12.32 | 0.979 ± 0.410** | 2.05 ± 1.34 | 2.38 ± 1.17*** | |
3-MC | 29.75 ± 9.12** | 17.20 ± 4.8* | 9.59 | 1.03 ± 0.33** | 0.616 ± 0.390 | 0.801 ± 0.290 | |
CLZ | Control | 199.0 ± 61.9 | 153.3 ± 43.5 | 0.94 | 0.380 ± 0.062 | 1.93 ± 1.22 | 0.999 ± 0.565 |
PCN | 23.25 ± 6.91* | 16.6 ± 4.9* | 4.09 | 0.732 ± 0.314 | 4.02 ± 2.74 | 3.96 ± 2.02 | |
3-MC | 4.645 ± 1.138* | 3.18 ± 0.91* | 7.09 | 1.04 ± 0.401*** | 9.06 ± 5.63** | 11.6 ± 5.2* | |
Metabolite | |||||||
1′-OH-MDZ | Control | 4.540 ± 0.449 | 11.88 ± 9.56 | 32.67 | 1.48 ± 0.88 | ||
PCN | 1.950 ± 0.528** | 1.81 ± 0.38** | 6.66 | 0.672 ± 0.276 | |||
3-MC | 3.532 ± 0.616** | 7.46 ± 1.69 | 22.81 | 1.29 ± 0.43 | |||
APAP | Control | 523.6 ± 190.8 | 671.6 ± 237.6 | 8.59 | 0.820 ± 0.233 | ||
PCN | 623.3 ± 140.5 | 367.8 ± 70.7** | 1.85 | 0.467 ± 0.172** | |||
3-MC | 336.8 ± 139.0 | 225.8 ± 62.7*** | 3.81 | 0.702 ± 0.227 | |||
DXO | Control | 29.9 ± 14.8 | 56.3 ± 10.3 | 15.56 | 1.17 ± 0.38 | ||
PCN | 15.8 ± 6.3 | 26.1 ± 8.7*** | 52.30 | 1.16 ± 0.43 | |||
3-MC | 14.6 ± 9.6 | 20.8 ± 46.5*** | 18.66 | 0.376 ± 0.181 | |||
4′-OH-DIC | Control | 240.2 ± 90.0 | 631.1 ± 250.2 | 32.76 | 1.85 ± 0.34 | ||
PCN | 747.5 ± 435.2** | 315.6 ± 133.9** | 14.77 | 1.28 ± 0.49 | |||
3-MC | 173.3 ± 61.0 | 362.4 ± 151.7 | 43.10 | 2.56 ± 1.19 | |||
6-OH-CLZ | Control | 60.7 ± 51.8 | 31.9 ± 12.8 | 12.24 | 0.422 ± 0.135 | ||
PCNa | 458.4 ± 134.1* | 171.1* | 0.01 | 0.357a | |||
3-MC | 33.7 ± 10.9 | 21.6 ± 2.8 | 37.70 | 0.620 ± 0.049 |
Extrap, extrapolated contribution to AUC; ND, not determined due to insufficient data points representing the elimination phase.
↵a Given incomplete data points because some were below quantification limits, a sparse data model was used.
↵b Values are given in nM for MDZ, PHE, DXM, APAP, DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM for DIC, CLZ, and 1′-OH-MDZ.
↵c Values are given in nM·h for MDZ, PHE, DXM, APAP, DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM·h for DIC, CLZ, and 1′-OH-MDZ.
↵* P < 0.001; **P < 0.05; ***P < 0.01 compared with the control (one-way analysis of variance with Bonferroni post hoc tests).