PDF(Pubmed)
Abstract：
BACKGROUND: Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties.
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.
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.
摘要：
背景：尽管近年来对鱼类疼痛和炎症的机制和控制的研究有所增加，由于缺乏有关镇痛药物的药理信息，镇痛药物的使用受到限制。托芬那酸是一种非甾体抗炎药，由于其低副作用和优越的药代动力学特性，可用于鱼类。
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（t1/2z），IM和口服途径为3.47、6.75和9.19h，分别。对于IV路线，稳定状态下的分布体积和全身清除率为0.09L/kg和0.03L/h/kg，分别。IM和口服给药的峰值血浆浓度和生物利用度分别为8.82和1.24µg/mL，和78.45%和21.48%，分别。虹鳟鱼中托芬那酸的平均血浆蛋白结合率为99.48％，与浓度无关。
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。
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。
