LACK OF EFFECT OF FOOD ON THE STEADY-STATE PHARMACOKINETICS OF BMS-181101, AN ANTIDEPRESSANT, IN HEALTHY-SUBJECTS

The effect of food on the pharmacokinetics of BMS-181101, a new anti-d epressant under development, was investigated in 12 healthy male volun teers at steady state. Each subject received a 15 mg oral dose of BMS- 181101 twice a day (q 12 h) for 11 days and a morning dose of BMS-1811 01 on day 12. Six subjects were randomly assigned to receive BMS-18110 1 under fasted conditions from days 1 to 6 and then crossed over to fe d conditions from days 7 to 12. The other six subjects received the re verse conditions, fed for days 1-6 and fasted for days 7-12. Serial bl ood samples were collected up to 12 h on days 6 and 12 following the a dministration of the morning dose. In addition, trough blood samples w ere collected on days 4, 5, 10, and 11 prior to the morning dose. Plas ma samples were analyzed for intact BMS-181101 using a validated high- performance liquid chromatography method with an electrochemical detec tor. BMS-181101 was well tolerated both with and without ingestion of food. The statistical evaluation of the C-min values indicated that st eady state of BMS-181101 was achieved by the fourth day of dosing rega rdless of whether the subject was fasted or fed. When BMS-181101 was a dministered with food, C-max was reduced by about 25% and t(max) was p rolonged by 1 h. However, AUC(tau), t(1/2), and time to attain steady state of BMS-181101 were not altered by ingestion of food. In summary, BMS-181101 can be given with food without adversely impacting the saf ety or pharmacokinetic profiles of the drug. (C) 1997 by John Wiley & Sons, Ltd.