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给山羊不同给药途径后托芬那酸的药代动力学。

Pharmacokinetics of tolfenamic acid in goats after different administration routes.

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Hatay Mustafa Kemal, Hatay, Turkey.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey.

出版信息

J Vet Pharmacol Ther. 2021 May;44(3):367-373. doi: 10.1111/jvp.12949. Epub 2021 Feb 9.

DOI:10.1111/jvp.12949
PMID:33560540
Abstract

The aim of this study was to determine the pharmacokinetics and bioavailability of tolfenamic acid in goats after intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at 2 mg/kg dose. In this study, eight clinically healthy goats were used. The study comprised four periods, according to a crossover design with at least a 15-day washout period between treatments. Plasma concentrations of tolfenamic acid were determined by HPLC-UV, and the pharmacokinetic parameters were estimated using a non-compartmental method. Following IV administration, terminal elimination half-life, volume of distribution at steady state, and total clearance were 1.60 h, 0.37 L/kg, and 0.27 L/h/kg, respectively. The mean peak plasma concentration following IM, SC, and PO administrations was 1.77, 1.22, and 0.30 μg/ml, respectively. The mean bioavailability following IM, SC, and PO administrations was 64.46, 55.43, and 19.46%, respectively. The PO route, which exhibits both the low plasma concentration and bioavailability, is not recommended in goats. The IV, IM, and SC routes, which show comparable pharmacokinetic profiles, may be proposed for use in goats. However, the multi-dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in the goat.

摘要

本研究旨在确定在 2mg/kg 剂量下,羊静脉(IV)、肌肉(IM)、皮下(SC)和口服(PO)给药后托芬那酸的药代动力学和生物利用度。在这项研究中,使用了 8 只临床健康的山羊。该研究包括四个时期,采用交叉设计,每种治疗之间至少有 15 天的洗脱期。采用 HPLC-UV 法测定托芬那酸的血浆浓度,采用非房室法估算药代动力学参数。IV 给药后,末端消除半衰期、稳态分布容积和总清除率分别为 1.60h、0.37L/kg 和 0.27L/h/kg。IM、SC 和 PO 给药后的平均峰血浆浓度分别为 1.77、1.22 和 0.30μg/ml。IM、SC 和 PO 给药后的平均生物利用度分别为 64.46%、55.43%和 19.46%。PO 途径表现出低血浆浓度和生物利用度,不推荐在山羊中使用。IV、IM 和 SC 途径显示出相似的药代动力学特征,可在山羊中使用。然而,需要进行多剂量和药效学研究,以更准确地确定其在山羊中的安全性和疗效。

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