title: A phase I study to characterize the multiple-dose pharmacokinetics, pharmacodynamics and safety of new enteric-coated triflusal formulations in healthy male volunteers.
abstract: OBJECTIVE
  An enteric-coated formulation of triflusal (triflusal EC), an antiplatelet agent, was developed to reduce the high incidence of gastrointestinal adverse events (AEs). The aim of this study is to compare the pharmacokinetics, pharmacodynamics and safety of triflusal EC with triflusal in healthy Korean male subjects to determine bioequivalence and non-inferiority for the purposes of marketing approval.
  
  
  METHODS
  A randomized, open-label, two-period, crossover study was conducted in 38 subjects. Either triflusal EC or triflusal was administered orally as a single 900 mg loading dose (day 1) followed by eight 600 mg/day maintenance doses on days 2 - 9, with a 13-day washout period. The plasma concentrations of 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), the predominant active metabolite of triflusal, were assessed after administration of the loading dose, using HPLC/MS/MS. The platelet aggregation response to arachidonic acid was determined using turbidimetric aggregometry.
  
  
  RESULTS
  The 90% CIs, for the geometric mean ratios of the log-transformed AUC(τ) and C(max) of HTB were seen to be within the predetermined range of 0.8 - 1.25. Triflusal EC was also shown to be non-inferior in its anti-aggregatory effect. No serious AEs were reported during this study.
  
  
  CONCLUSIONS
  The pharmacokinetic and pharmacodynamic profiles of the two triflusal formulations met the requirements for bioequivalence and non-inferiority, respectively. Both formulations were well tolerated.
authors.affiliation: Kyungpook National University Graduate School and Hospital, Department of Biomedical Science and Clinical Trial Center, 200 Dongduk-Ro, Jung-gu, Daegu, 700-721, Republic of Korea.
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Mi-sun
authors.initials: MS
authors.lastname: Lim
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Seong
authors.forename: Joomi
authors.initials: J
authors.lastname: Lee
authors.forename: Jeonghyeon
authors.initials: J
authors.lastname: Park
authors.forename: Jeong Ju
authors.initials: JJ
authors.lastname: Seo
authors.forename: Hwi-yeol
authors.initials: HY
authors.lastname: Yun
authors.forename: In-hwan
authors.initials: IH
authors.lastname: Baek
authors.forename: Kwang-il
authors.initials: KI
authors.lastname: Kwon
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D044466:Asian People; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012459:Salicylates / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; D016718:Arachidonic Acid; C033502:4-trifluoromethylsalicylic acid