title: Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans.
abstract: BACKGROUND
  Development of niacin-like agents that favorably affect lipids with an improved flushing profile would be beneficial.
  
  
  OBJECTIVE
  To evaluate a niacin receptor partial agonist, MK-0354, in Phase I and II studies.
  
  
  METHODS
  The pharmacokinetic/pharmacodynamic effects of single and multiple doses (7 days) of MK-0354 (300-4000 mg) were evaluated in two Phase I studies conducted in healthy men. A Phase II study assessed the effects of MK-0354 2.5 g once daily on lipids during 4 weeks in 66 dyslipidemic patients.
  
  
  RESULTS
  MK-0354 single doses up to 4000 mg and multiple doses (7 days) up to 3600 mg produced robust dose-related reductions in free fatty acid (FFA) over 5 hours. Single doses of MK-0354 300 mg and extended release-niacin (Niaspan) 1 g produced comparable reductions in FFA. Suppression of FFA following 7 daily doses of MK-0354 was similar to that after a single dose. In the Phase II study, MK-0354 2.5 g produced little flushing but no clinically meaningful effects on lipids (placebo-adjusted percent change: high-density lipoprotein cholesterol, 0.4%, 95% confidence interval -5.2 to 6.0; low-density lipoprotein cholesterol, -9.8%, 95% confidence interval -16.8 to -2.7; triglyceride, -5.8%, 95% confidence interval -22.6 to 11.9).
  
  
  CONCLUSIONS
  Treatment with MK-0354 for 7 days resulted in plasma FFA suppression with minimal cutaneous flushing. However, 4 weeks of treatment with MK-0354 failed to produce changes in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or triglycerides.
authors.affiliation: Merck & Co., Inc., 126 East Lincoln Avenue, PO Box 2000, Rahway, NJ 07065-0900, USA.
authors.forename: Eseng
authors.initials: E
authors.lastname: Lai
authors.forename: M Gerard
authors.initials: MG
authors.lastname: Waters
authors.forename: James R
authors.initials: JR
authors.lastname: Tata
authors.forename: Waldemar
authors.initials: W
authors.lastname: Radziszewski
authors.forename: Inna
authors.initials: I
authors.lastname: Perevozskaya
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Larissa
authors.initials: L
authors.lastname: Wenning
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Connolly
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
authors.forename: Amy O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Yale
authors.initials: Y
authors.lastname: Mitchel
authors.forename: John F
authors.initials: JF
authors.lastname: Paolini