Pharmacokinetics and brain distribution of zolpidem in the rat after acute and chronic administration.

The pharmacokinetics of zolpidem were studied after single dose, administered for either 7 or 28 days to rats. Thirty minutes after the last dose, animals were killed and the brain removed. The highest concentrations in plasma, which were observed at the first sampling time (0.5 h) were 2341 +/- 540 (day 0), 1956 +/- 325 (day 7) and 2908 +/- 1369 ng mL-1 (day 28). Corresponding AUC values of 1742 +/- 488, 1583 +/- 422 and 2683 +/- 1249 ng mL-1 h were found. MRT increased significantly from 0.46 +/- 0.06 h on day 0 to 0.67 +/- 0.02 h on day 28. The cerebral levels showed no significant change during the chronic administration (766 +/- 285, 685 +/- 171 and 887 +/- 264 ng g-1, respectively). No modification of the principal kinetic parameters was detected up to the 28th day of treatment.