Analyte | Treatment | Cmaxb | AUC0→∞c | Extrap | t1/2 | CL/F | Vz/F |
---|---|---|---|---|---|---|---|
% | h | l/h | liters | ||||
Substrate | |||||||
MDZ | Control | 290.8 ± 89.7 | 347.3 ± 91.2 | 10.00 | 0.858 ± 0.297 | 0.282 ± 0.080 | 0.357 ± 0.160 |
KTZ | 472.8 ± 214.9 | 978.2 ± 34.8*** | 22.17 | 1.26 ± 0.65 | 0.108 ± 0.047*** | 0.178 ± 0.065** | |
α-NF | 208.7 ± 51.3 | 258.0 ± 29.7 | 7.12 | 0.739 ± 0.174 | 0.361 ± 0.044 | 0.378 ± 0.070 | |
PHE | Control | 2.182 ± 0.851 | 613.7 ± 170.8 | 2.74 | 0.228 ± 0.055 | 0.803 ± 0.169 | 0.259 ± 0.064 |
KTZ | 0.775 ± 0.666* | 207.1 ± 161.5 | 6.31 | 0.213 ± 0.123 | 5.03 ± 5.12 | 1.20 ± 0.91** | |
α-NF | 2.167 ± 0.445 | 1.454 ± 0.430*** | 1.93 | 0.440 ± 0.190** | 0.344 ± 0.087 | 0.211 ± 0.081 | |
DXM | Control | 592.8 ± 226.0 | 1.596 ± 0.490 | 39.68 | 1.96 ± 0.45 | 14.4 ± 6.2 | 37.7 ± 8.6 |
KTZ | 974.0 ± 472.0 | 4.011 ± 2.324** | 45.32 | 2.36 ± 0.46 | 6.40 ± 4.55 | 19.8 ± 12.0 | |
α-NF | 381.0 ± 147.7 | 1.192 ± 0.651 | 34.13 | 1.76 ± 0.54 | 29.7 ± 22.7 | 62.7 ± 34.2 | |
DIC | Control | 9.247 ± 3.762 | 14.68 ± 7.06 | 20.57 | 1.21 ± 0.37 | 0.386 ± 0.152 | 0.634 ± 0.260 |
KTZ | 20.32 ± 10.45** | 52.77 ± 27.62* | 39.30 | 1.90 ± 0.43 | 0.0866 ± 0.106 | 0.200 ± 0.190 | |
α-NF | 8.218 ± 4.138 | 9.786 ± 6.136 | 22.13 | 1.51 ± 0.86 | 0.553 ± 0.331 | 1.28 ± 0.59** | |
CLZ | Control | 41.91 ± 11.47 | 45.03 ± 5.35 | 6.73 | 0.660 ± 0.237 | 1.12 ± 1.03 | 0.910 ± 0.651 |
KTZ | 109.5 ± 58.4** | 119.5 ± 50.42** | 13.2 | 0.767 ± 0.173 | 0.218 ± 0.104 | 0.228 ± 0.112** | |
α-NF | 71.29 ± 37.52 | 91.55 ± 30.90 | 7.40 | 0.688 ± 0.240 | 0.384 ± 0.216 | 0.329 ± 0.089 | |
Metabolite | |||||||
1′-OH-MDZ | Control | 3.758 ± 0.750 | 10.19 ± 1.89 | 28.73 | 1.49 ± 0.22 | ||
KTZ | 2.992 ± 0.628 | 17.72 ± 9.03 | 58.95 | 3.70 ± 1.64* | |||
α-NF | 4.505 ± 0.491 | 13.27 ± 4.39 | 34.56 | 1.73 ± 0.53 | |||
APAP | Control | 500.0 ± 69.4 | 529.6 ± 59.5 | 1.86 | 0.475 ± 0.097 | ||
KTZ | 381.5 ± 186.2 | 364.4 ± 384.3** | 2.64 | 0.537 ± 0.087 | |||
α-NF | 362.2 ± 140.7 | 379.2 ± 80.1* | 3.11 | 0.529 ± 0.116 | |||
DXO | Control | 53.6 ± 19.4 | 87.9 ± 9.4 | 16.40 | 1.08 ± 0.45 | ||
KTZ | 25.3 ± 10.7** | 61.5 ± 19.2** | 30.00 | 1.34 ± 0.21 | |||
α-NF | 40.1 ± 14.3 | 56.6 ± 18.6 | 20.88 | 0.948 ± 0.33 | |||
4′-OH-DIC | Control | 141.6 ± 57.5 | 171.5 ± 56.3 | 14.61 | 1.09 ± 0.25 | ||
KTZ | 36.4 ± 21.3* | 97.8 ± 41.3** | 30.05 | 1.56 ± 0.17** | |||
α-NFa | 180.8 | 8.4 | 3.20 | 2.10 | |||
6-OH-CLZ | Control | 43.33 ± 4.62 | 40.7 ± 10.4 | 16.77 | 0.526 ± 0.083 | ||
KTZ | 16.47 ± 4.73*** | 51.4 ± 19.2 | 33.02 | 4.16 ± 1.72** | |||
α-NFa | 5.043 | 7.7 | 66.4 | 1.15 |
Extrap, extrapolated contribution to AUC.
↵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, DXM, APAP, DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM for PHE, DIC, CLZ, and 1′-OH-MDZ.
↵c Values are given in nM·h for MDZ, PHE (control and KTZ) APAP, DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM·h for PHE (α-NF), DXM, DIC, CLZ, and 1′-OH-MDZ.
↵* P < 0.01; **P < 0.05; ***P < 0.001 compared with the control (one-way analysis of variance with Bonferroni post hoc tests).