TABLE 1.
Pharmacokinetic profiles of XAP044 in mice and rats
The absorption and disposition parameters were estimated by a noncompartmental analysis of the mean blood concentration (n = 3) versus time profile after p.o. and i.v. administration. The apparent terminal phase rate constant was determined by choosing the last three data points from the log-linear regression of the blood concentrations versus time curve and was used for the extrapolation of the area under the curve (AUC) to infinity. The absolute oral bioavailability (BAV) was calculated by dividing the dose-normalized (d.n.) AUC after p.o. administration by the respective AUC after i.v. administration assuming linear pharmacokinetics between the intravenous and oral doses.
| Parameter/species | Mouse | Rat |
|---|---|---|
| Doses (i.v./p.o. (mg/kg)) | 1.0/3.0 | 3.0/10.0 |
| Matrix | Blood | Plasma |
| Strain, gender | C57BL/6, male | Sprague-Dawley, male |
| Cl (ml/min/kg) | 76 | 12 |
| Vss (liter/kg) | 0.9 | 3.0 |
| MRT (h) | 0.2 | 4.3 |
| t½ (h) | 0.4 | 4.5 |
| AUC i.v., d.n. (nmol·h) | 576 | 3691 |
| AUC p.o., d.n. (nmol·h) | 95 | 1907 |
| BAV (%) | 17 | 52 |
| Cmax d.n. (nmol) | 55 | 140 |
| tmax (h) | 0.3 | 8 |
| Brain/blood (mouse) or brain/plasma (rat) ratio | 0.4–0.6 | 0.4–0.6 |