Ramis J, Mis R, Forn J
Research Center, J. Uriach & Cia, S.A. Barcelona, Spain.
Eur J Drug Metab Pharmacokinet. 1991 Oct-Dec;16(4):261-8. doi: 10.1007/BF03189970.
The methods for determining plasma concentrations of triflusal (2-acetoxy-4-trifluoromethyl benzoic acid) that have been described, do not distinguish between the drug and its main metabolite HTB (2-hydroxy-4-trifluoromethyl benzoic acid). In the present study, we have developed a new analytical technique based on HPLC that enabled us to carry out a pharmacokinetic study of the drug and its metabolite in animals. An intravenous or oral dose of 50 mg/kg was administered to male Sprague-Dawley rats, and 15 mg/kg was administered to beagle dogs. Plasma levels of triflusal and HTB were determined. In rats, triflusal was quickly eliminated from plasma with a biological half-life (t1/2) of 2.7 min and a clearance (Cl) of 73.4 (ml/kg)/min. The elimination of HTB was much slower with a t1/2 of 21.5 h and a Cl of 5.1 (mg/kg)/h. The maximum concentration (Cmax) of triflusal in rats after an oral administration was 8.1 +/- 2.0 micrograms/ml reached between 2.5 and 10 min. The Cmax of HTB was 237.7 micrograms/ml and was achieved at 0.7 h. The bioavailability of triflusal in rats was only 10.6% while the bioavailability of HTB was more than 100% indicating an important first pass effect. In dogs the t1/2 of triflusal was 14.4 +/- 5.9 min and the Cl was 25.1 +/- 4.7 (ml/kg)/min. HTB was also eliminated very slowly with a t1/2 of 71.1 +/- 12.5 h and a Cl of 2.4 +/- 0.3 (ml/kg)/h. The Cmax of triflusal in dogs was 13.3 +/- 2.9 micrograms/ml and was reached after 19.2 +/- 6.1 min (tmax).(ABSTRACT TRUNCATED AT 250 WORDS)
已描述的测定曲氟柳（2 - 乙酰氧基 - 4 - 三氟甲基苯甲酸）血浆浓度的方法，无法区分该药物及其主要代谢物HTB（2 - 羟基 - 4 - 三氟甲基苯甲酸）。在本研究中，我们开发了一种基于高效液相色谱的新分析技术，使我们能够在动物体内对该药物及其代谢物进行药代动力学研究。给雄性斯普拉 - 道利大鼠静脉注射或口服50mg/kg的剂量，给比格犬口服15mg/kg的剂量。测定曲氟柳和HTB的血浆水平。在大鼠中，曲氟柳从血浆中快速消除，生物半衰期（t1/2）为2.7分钟，清除率（Cl）为73.4（ml/kg）/分钟。HTB的消除则慢得多，t1/2为21.5小时，Cl为5.1（mg/kg）/小时。大鼠口服给药后曲氟柳的最大浓度（Cmax）为8.1±2.0微克/毫升，在2.5至10分钟之间达到。HTB的Cmax为237.7微克/毫升，在0.7小时时达到。曲氟柳在大鼠中的生物利用度仅为10.6%，而HTB的生物利用度超过100%，表明存在重要的首过效应。在犬中，曲氟柳的t1/2为14.4±5.9分钟，Cl为25.1±4.7（ml/kg）/分钟。HTB的消除也非常缓慢，t1/2为71.1±12.5小时，Cl为2.4±0.3（ml/kg）/小时。犬中曲氟柳的Cmax为13.3±2.9微克/毫升，在19.2±6.1分钟（tmax）后达到。（摘要截短至250字）
