Pharmacokinetic parameters and liver weights after once-daily dosing of GW333 for 14 days to rats
Blood samples were collected from six rats on the first and last day of dosing at 0.5, 1.5, 4, 8, and 24 h after dose administration. GW3333 plasma concentrations were determined by LC/MS-MS as described under Materials and Methods. Maximum plasma concentration (Cmax) was the highest mean concentration of GW3333 found in the collected samples. A composite area under the plasma concentration-time curve (AUC) was calculated by the trapezoidal method. Livers were collected 24 h after the last daily dose of vehicle or GW3333.
Daily Dose | Sample Day | Cmax | AUCa | % Decrease | % Increase |
|---|---|---|---|---|---|
| mg/kg | μM | ng · h/ml | AUC | relative liver weight | |
| 50 | Day 1 | 11.5 | 17,300 | ||
| Day 14 | 9.6 | 10,300 | 40 | 11 | |
| 150 | Day 1 | 26.2 | 64,900 | ||
| Day 14 | 15.3 | 32,200 | 50 | 20 | |
| 500 | Day 1 | 54.6 | 319,900 | ||
|
|
Day 14
|
24.7
|
124,100
|
61
|
36
|
↵ a Day 1, AUC0-∞; day 14, AUC0-24 h.