TABLE 1.
Comparison of Pharmacokinetics Parameters of the Probe Drugs
| Group | Cmax (μg/mL) | AUC (min·μg/mL) | AUCmetabolite/AUCdrug | t1/2 (min) | |
|---|---|---|---|---|---|
| Caffeine | WT | 2.0 ± 1.1 | 491.1 ± 91.3 | 1.06 ± 0.03 | 158 ± 71 |
| ob/ob | 4.9 ± 0.9 * | 1418.0 ± 341.8 * | 0.46 ± 0.17 * | 342 ± 236 | |
| ob/ob MCD | 5.1 ± 1.2 * | 1431.0 ± 325.7 * | 0.67 ± 0.34 * | 221 ± 131 | |
| Omeprazole | WT | 0.6 ± 0.7 | 36.2 ± 31.7 | 1.28 ± 0.76 | 70 ± 45 |
| ob/ob | 3.1 ± 1.9 | 314.5 ± 195.4 | 0.36 ± 0.18 * | 56 ± 13 | |
| ob/ob MCD | 4.7 ± 4.8 | 486.8 ± 450.7 | 0.52 ± 0.34 * | 77 ± 31 | |
| Midazolam | WT | 0.30 ± 0.15 | 36.7 ± 11.8 | 6.70 ± 0.69 | 88 ± 38 |
| ob/ob | 0.26 ± 0.10 | 47.9 ± 18.5 | 7.30 ± 2.60 | 140 ± 53 | |
| ob/ob MCD | 0.47 ± 0.27 | 66.1 ± 37.2 | 5.71 ± 3.33 | 113 ± 32 | |
| Losartan | WT | 0.15 ± 0.13 | 64.6 ± 115.1 | 1.38 ± 1.00 | 114 ± 51 |
| ob/ob | 0.94 ± 1.12 | 123.9 ± 109.0 | 3.48 ± 1.97 | 90 ± 32 | |
| ob/ob MCD | 7.8 ± 10.50 | 1006.0 ± 1135.0 | 0.68 ± 0.41 # | 132 ± 69 | |
| Dextromethorphan | WT | 0.08 ± 0.03 | 19.1 ± 7.8 | 0.59 ± 0.14 | 123 ± 30 |
| ob/ob | 0.17 ± 0.10 | 37.0 ± 23.3 | 0.56 ± 0.19 | 120 ± 35 | |
| ob/ob MCD | 0.36 ± 0.43 | 65.9 ± 55.3 | 0.71 ± 0.28 | 172 ± 131 |
Noncompartmental analysis was applied to calculate AUC, terminal half-life (t1/2), maximum plasma concentration (Cmax), and the AUC ratio was calculated based on the AUC value of the metabolite and the parent drug.
Data represent mean ± SEM. WT n = 5, ob/ob n = 5, ob/ob MCD n = 5. One-way ANOVA with Tukey’s multiple comparisons posttest were performed to determine the statistical significance
*
Indicates a significant difference between ob/ob and/or ob/ob MCD with WT mice, whereas # indicates a significant difference between ob/ob and ob/ob MCD mice.