PHARMACOKINETICS AND BRAIN DISTRIBUTION OF ZOLPIDEM IN THE RAT AFTER ACUTE AND CHRONIC ADMINISTRATION

The pharmacokinetics of zolpidem were studied after single dose, admin istered for either 7 or 28 days to rats. Thirty minutes after the last dose, animals were killed and the brain removed. The highest concentr ations 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 n g mL(-1) (day 28). Correspond ing AUC values of 1742 +/- 488, 1583 +/- 422 and 2683 +/- 1249 ng mL(-1) h were found. MRT increased significa ntly from 0.46 +/- 0.06 h on day 0 to 0.67 +/- 0.02 h on day 28. The c erebral levels showed no significant change during the chronic adminis tration (766 +/- 285 685 +/- 171 and 887 +/- 264 ng g(-1), respectivel y). No modification of the principal kinetic parameters was detected u p to the 28th day of treatment.