Davis J L, Papich M G, Morton A J, Gayle J, Blikslager A T, Campbell N B
Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27606, USA.
J Vet Pharmacol Ther. 2007 Feb;30(1):43-8. doi: 10.1111/j.1365-2885.2007.00811.x.
The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally, in vitro cyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two-way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3-week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half-life (t(1/2)) of 2.67 h, volume of distribution (Vd) of 0.29 L/kg and clearance (Cl) of 234.87 mL/h kg. Following oral administration, the average maximum plasma concentration (Cmax)) was 32.57 mug/mL with a t(1/2) of 3.02 h. Bioavailability was approximately 77.02%. Results of in vitro COX selectivity assays showed that etodolac was only slightly selective for COX-2 with a COX-1/COX-2 selectivity ratio effective concentration (EC)50 of 4.32 and for EC80 of 4.77. This study showed that etodolac is well absorbed in the horse after oral administration, and may offer a useful alternative for anti-inflammatory treatment of various conditions in the horse.
本研究的目的是确定依托度酸在对六匹马进行口服和静脉给药后的药代动力学。此外，使用马全血进行了体外环氧化酶（COX）选择性测定。采用随机双向交叉设计，给马口服或静脉注射依托度酸（20mg/kg），洗脱期至少为3周。给药后采集血浆样本，采用带紫外检测的高压液相色谱法进行分析。静脉给药后，依托度酸的平均血浆半衰期（t(1/2)）为2.67小时，分布容积（Vd）为0.29L/kg，清除率（Cl）为234.87mL/h·kg。口服给药后，平均最大血浆浓度（Cmax）为32.57μg/mL，t(1/2)为3.02小时。生物利用度约为77.02%。体外COX选择性测定结果表明，依托度酸对COX-2仅有轻微选择性，COX-1/COX-2选择性比率的有效浓度（EC）50为4.32，EC80为4.77。本研究表明，依托度酸在马口服后吸收良好，可能为马各种病症的抗炎治疗提供一种有用的替代药物。
