Pharmacokinetic parameters for drug cocktail administered to WT and Cyp2c/2d/3a KO mice
A five-drug cocktail was administered to WT (n = 5), Cyp3a KO (n = 3), and Cyp2c/2d/3a KO (n = 4) mice and blood samples were taken for analysis and drug levels determined as detailed in Materials and Methods. Pharmacokinetic parameters were derived from the WinNonLin software package, and data are shown as mean ± S.D.
| Drug | WT | Cyp2c/2d/3a KO | Cyp3a KO |
|---|---|---|---|
| Caffeine | |||
| Cmax (µg/ml) | 3.11 ± 1.08 | 2.33 ± 0.19 | |
| Half-life (min) | 71.3 ± 10.9 | 72.7 ± 25.0 | |
| AUC0–8h (min⋅µg/ml) | 411.2 ± 43.3 | 351.8 ± 73.6 | |
| AUC0–inf (min⋅µg/ml) | 415.4 ± 43.0 | 355.9 ± 72.6 | |
| Cl (ml/min/kg) | 12.1 ± 1.33 | 14.7 ± 3.12 | |
| Bupropion | |||
| Cmax (µg/ml) | 0.74 ± 0.30 | 0.16 ± 0.02** | |
| Half-life (min) | 72.3 ± 18.6 | 169.6 ± 53.6** | |
| AUC0–8h (min⋅µg/ml) | 95.3 ± 26.3 | 12.1 ± 3.21*** | |
| AUC0–nf (min⋅µg/ml) | 97.2 ± 26.8 | 13.2 ± 2.90*** | |
| Cl (ml/min/kg) | 331.6 ± 106.8 | 2837 ± 805*** | |
| Tolbutamide | |||
| Cmax (µg/ml) | 54.2 ± 17.1 | 29.5 ± 14.1* | |
| AUC0–8h (min⋅µg/ml) | 11,287 ± 2549 | 10,304 ± 2937 | |
| Bufuralol | |||
| Cmax (µg/ml) | 0.02 ± 0.01 | 0.30 ± 0.04*** | |
| AUC0–8h (min⋅µg/ml) | 3.54 ± 2.13 | 93.1 ± 12.6*** | |
| Midazolam | |||
| Cmax (µg/ml) | 0.09 ± 0.03 | 0.30 ± 0.03** | 0.14 ± 0.06 |
| Half-life (min) | 84.9 ± 12.1 | 81.5 ± 16.1 | 136 ± 89 |
| AUC0–8h (min⋅µg/ml) | 7.31 ± 3.47 | 29.6 ± 11.1* | 14.2 ± 14.5 |
| AUC0–inf (min⋅µg/ml) | 7.56 ± 3.46 | 30.2 ± 11.0* | 14.9 ± 14.5 |
| Cl (ml/min/kg) | 469.7 ± 205.8 | 127.5 ± 57.7* | 366 ± 279 |
↵* P < 0.05; **P < 0.01; ***P < 0.005 WT to Cyp2c/2d/3a KO mice.