Table 3. Pharmacokinetic parameters of simvastatin and simvastatin acid after oral (20 mg/kg) and intravenous (2 mg/kg) administration of simvastatin to DM, HFD, and CON rats.
| Parameters | CON | HFD | DM |
|---|---|---|---|
| Oral administration | |||
| Simvastatin | |||
| Tmax (h) | 1.38±0.63 | 0.75±0.84 | 0.75±0.25 |
| Cmax (ng/mL) | 252.50±29.91 | 197.28±65.64 | 181.31±14.14c |
| AUC0–∞ (ng·h·mL−1) | 1399.40±143.81 | 820.01±72.45c | 1003.79±40.92cf |
| T1/2 (h) | 7.62±4.80 | 6.53±2.59 | 5.90±2.33 |
| MRT (h) | 12.66±6.01 | 10.60±2.71 | 10.41±2.89 |
| Simvastatin acid | |||
| Tmax (h) | 1.06±0.72 | 1.25±0.29 | 0.95±0.37 |
| Cmax (ng/mL) | 301.75±64.33 | 147.63±10.41c | 167.70±40.59c |
| AUC0–∞ (ng·h·mL−1) | 1312.86±210.40 | 727.47±49.27c | 744.10±91.45c |
| T1/2 (h) | 3.79±0.95 | 4.40±1.53 | 3.77±1.59 |
| MRT (h) | 6.64±1.01 | 7.64±0.77 | 7.23±2.14 |
| Intravenous administration | |||
| Simvastatin | |||
| AUC120 (ng·h·mL−1) | 388.43±36.35 | 507.57±63.81 | 289.72±33.87cf |
| AUC0–∞ (ng·h·mL−1) | 466.27±75.18 | 642.07±130.08 | 369.12±49.45f |
| T1/2 (min) | 42.45±9.17 | 52.96±21.48 | 47.38±12.20 |
| Cl (L·h−1·kg−1) | 4.36±0.61 | 3.21±0.64b | 5.49±0.72f |
| MRT (min) | 66.42±12.8 | 80.88±20.20 | 73.18±22.72 |
| Simvastatin acid | |||
| AUC120 (ng·h·mL−1) | 843.17±235.83 | 1225.17±316.67 | 486.33±53.50bf |
| AUC0–∞ (ng·h·mL−1) | 946.33±300.33 | 1294.00±329.67 | 492.33±53.83bf |
| T1/2 (min) | 31.55±9.78 | 29.90±3.98 | 20.39±3.82bf |
| MRT (min) | 54.17±8.58 | 44.78±6.50 | 30.82±5.98cf |
Data were expressed as mean±SD of 6 rats, bP<0.05, cP<0.01 vs CON rats. fP<0.01 vs HFD rats.