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Pharmacokinetics of tolfenamic acid in green sea turtles (Chelonia mydas) after intravenous and intramuscular administration.
Journal of Veterinary Pharmacology and Therapeutics ( IF 1.5 ) Pub Date : 2020-06-10 , DOI: 10.1111/jvp.12885
Natsuda Raweewan 1 , Thanaphan Chomcheun 2 , Weerapong Laovechprasit 2 , Oranee Jongkolpath 2 , Narumol Klangkaew 1 , Napasorn Phaochoosak 1 , Mario Giorgi 3 , Amnart Poapolathep 1 , Saranya Poapolathep 1
Affiliation  

The present study aimed to evaluate the pharmacokinetic features of tolfenamic acid (TA) in green sea turtles, Chelonia mydas. Green sea turtles were administered single either intravenous (i.v.) or intramuscular (i.m.) injection of TA, at a dose of 4 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 168 hr. The plasma concentrations of TA were measured using a validated liquid chromatography tandem mass spectrometry method. Tolfenamic acid plasma concentrations were quantifiable for up to 168 hr after i.v. and i.m. administration. The concentration of TA in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The Cmax values of TA were 55.01 ± 8.34 µg/ml following i.m. administration. The elimination half‐life values were 32.76 ± 4.68 hr and 53.69 ± 3.38 hr after i.v. and i.m. administration, respectively. The absolute i.m. bioavailability was 72.02 ± 10.23%, and the average binding percentage of TA to plasma protein was 19.43 ± 6.75%. Based on the pharmacokinetic data, the i.m. administration of TA at a dosage of 4 mg/kg b.w. might be sufficient to produce a long‐lasting anti‐inflammatory effect (7 days) for green sea turtles. However, further studies are needed to determine the clinical efficacy of TA for treatment of inflammatory disease after single and multiple dosages.

中文翻译:

静脉和肌肉内给药后,甲苯戊酸在绿海龟(Chelonia mydas)中的药代动力学。

本研究旨在评估托芬那酸(TA)在绿海龟(Chelonia mydas)中的药代动力学特征绿海龟以4 mg / kg体重(bw)的剂量静脉内(iv)或肌内(im)注射一次TA。在预先指定的时间(长达168小时)收集血液样本。使用经过验证的液相色谱串联质谱法测量TA的血浆浓度。静脉和即时给药后,托芬那酸血浆浓度可长达168小时。使用非隔离室模型,用药代动力学分析了实验绿海龟中TA相对于时间的浓度。该Ç最大im给药后TA的值为55.01±8.34 µg / ml。静脉和肌内注射后,消除半衰期值分别为32.76±4.68小时和53.69±3.38小时。绝对的绝对生物利用度为72.02±10.23%,TA与血浆蛋白的平均结合率为19.43±6.75%。根据药代动力学数据,以4 mg / kg bw的剂量对TA进行im给药可能足以对绿海龟产生持久的抗炎作用(7天)。然而,需要进一步的研究来确定单剂和多剂后TA治疗炎性疾病的临床疗效。
更新日期:2020-06-10
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