OBJECTIVE: The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C.
METHODS: The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis.
RESULTS: The elimination half-life (t1/2ʎz) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent.
CONCLUSIONS: While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
目的:药代动力学,在单一血管内(IV)后研究了托芬那酸的生物利用度和血浆蛋白结合,在13±0.5°C下,在虹鳟鱼中肌内(IM)和口服2mg/kg。
方法:在总共234条虹鳟鱼(Oncorhynchusmykiss)上进行了实验。托芬那酸通过静脉注射给鱼,IM和口服途径,剂量为2mg/kg。在13个不同的采样时间采集血样,直到给药后72小时。使用高压液相色谱-紫外线(UV)定量托芬那酸的血浆浓度,并使用非房室分析评估药代动力学参数。
结果:托芬那酸用于IV的消除半衰期(t1/2
结论:当IM路由时,同时表现出很高的血浆浓度和生物利用度,可用于虹鳟鱼,由于血浆浓度和生物利用度低,不推荐口服.然而,有必要证明托芬那酸在虹鳟鱼中的药效学活性。