Lack of effect of food on the steady state pharmacokinetics of BMS-181101, an antidepressant, in healthy subjects

Biopharm Drug Dispos. 1997 Oct;18(7):585-93. doi: 10.1002/(sici)1099-081x(199710)18:7<585::aid-bdd43>3.0.co;2-l.

Abstract

The effect of food on the pharmacokinetics of BMS-181101, a new anti-depressant under development, was investigated in 12 healthy male volunteers 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-181101 on day 12. Six subjects were randomly assigned to receive BMS-181101 under fasted conditions from days 1 to 6 and then crossed over to fed conditions from days 7 to 12. The other six subjects received the reverse conditions, fed for days 1-6 and fasted for days 7-12. Serial blood samples were collected up to 12 h on days 6 and 12 following the administration of the morning dose. In addition, trough blood samples were collected on days 4, 5, 10, and 11 prior to the morning dose. Plasma samples were analyzed for intact BMS-181101 using a validated high-performance liquid chromatography method with an electrochemical detector. BMS-181101 was well tolerated both with and without ingestion of food. The statistical evaluation of the Cmin values indicated that steady state of BMS-181101 was achieved by the fourth day of dosing regardless of whether the subject was fasted or fed. When BMS-181101 was administered with food, Cmax was reduced by about 25% and tmax was prolonged by 1 h. However, AUCtau, t1/2, 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 safety or pharmacokinetic profiles of the drug.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacokinetics*
  • Area Under Curve
  • Cross-Over Studies
  • Diet
  • Fasting
  • Food-Drug Interactions*
  • Humans
  • Male
  • Piperazines / administration & dosage
  • Piperazines / pharmacokinetics*
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics*

Substances

  • Antidepressive Agents
  • BMS 181101
  • Piperazines
  • Pyrimidines