Anacetrapib blood pharmacokinetic parameters on days 1 and 42 of dosing
Anacetrapib was dosed orally once daily to WT-lean, WT-DIO, NFR-lean, and NFR-DIO mice at 10 mg/kg for 42 days. On days 1 and 42, five animals from each subgroup underwent serial blood sampling for a full blood pharmacokinetic profile. Blood concentrations were measured as described in Methods. Pharmacokinetic parameters were calculated using WinNonlin 5.1 software. Numbers represent mean and S.E. from n = 5 mice.
| WT Lean | WT DIO | NFR Lean | NFR DIO | |
|---|---|---|---|---|
| Day 1 AUC0–∞ (μM*h) | 8.3 ± 2.1 | 35 ± 4.0 | 13 ± 1.3 | 51 ± 11 |
| AUC0–24h (μM*h) | 7.8 ± 1.7 | 29 ± 3.8 | 9.8 ± 0.8 | 25 ± 6.2 |
| Cmax (μM) | 2.7 ± 0.8 | 5.2 ± 1.5 | 2.8 ± 0.8 | 5.0 ± 1.3 |
| T 1/2 (h) | 14 ± 4.6 | 17 ± 3.3 | 23 ± 6.1 | 60 ± 25 |
| Day 42 | ||||
| AUC0–∞ (μM*h) | 14 ± 1.2 | 93 ± 28 | 48 ± 26 | 118 ± 33 |
| AUC0–24h (μM*h) | 9.2 ± 0.8 | 44 ± 4.5 | 13 ± 1.3 | 45 ± 8.5 |
| Cmax (μM) | 2.7 ± 0.4 | 6.1 ± 1.3 | 3.4 ± 0.9 | 6.8 ± 1.3 |
| T 1/2 (h) | 74 ± 31 | 63 ± 36 | 152 ± 127a | 66 ± 34a |
↵a Some uncertainty in t½ calculation, due to secondary peaks in blood concentration time profile.