A Phase I study to characterize the multiple-dose pharmacokinetics, pharmacodynamics and safety of new enteric-coated triflusal formulations in healthy male volunteers
| Autor: | Jeonghyeon Park, Jeong Ju Seo, Mi-sun Lim, Joomi Lee, Sook Jin Seong, Young-Ran Yoon, Kwang-il Kwon, In-hwan Baek, Hwi-yeol Yun, Hae Won Lee |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Platelet Aggregation Chemistry Pharmaceutical Administration Oral Pharmacology Bioequivalence Toxicology Loading dose Young Adult Asian People Pharmacokinetics Tandem Mass Spectrometry medicine Humans Adverse effect Chromatography High Pressure Liquid Active metabolite Arachidonic Acid Cross-Over Studies Dose-Response Relationship Drug Chemistry General Medicine Crossover study Salicylates Therapeutic Equivalency Pharmacodynamics Triflusal Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Expert Opinion on Drug Metabolism & Toxicology. 7:1471-1479 |
| ISSN: | 1744-7607 1742-5255 |
| DOI: | 10.1517/17425255.2011.630661 |
| Popis: | 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.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.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.The pharmacokinetic and pharmacodynamic profiles of the two triflusal formulations met the requirements for bioequivalence and non-inferiority, respectively. Both formulations were well tolerated. |
| Databáze: | OpenAIRE |
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