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Lack of effect of food on the steady state pharmacokinetics of BMS‐181101, an antidepressant, in healthy subjects
Author(s) -
Srinivas Nuggehally R.,
Shyu Wen C.,
Lee James,
Greene Douglas S.,
Barbhaiya Rashmi H.
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199710)18:7<585::aid-bdd43>3.0.co;2-l
Subject(s) - pharmacokinetics , antidepressant , pharmacology , steady state (chemistry) , medicine , chemistry , hippocampus
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 C min 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, C max was reduced by about 25% and t max was prolonged 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 safety or pharmacokinetic profiles of the drug. © 1997 John Wiley & Sons, Ltd.