Jones Emery, Walton Stuart A, Davis Jennifer, Council-Troche McAlister
Desert Veterinary Medical Specialist, Phoenix, AZ, United States.
Department of Small Animal Clinical Science, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
Front Vet Sci. 2024 Sep 25;11:1482871. doi: 10.3389/fvets.2024.1482871. eCollection 2024.
To determine whether intravenous lipid emulsion (ILE) therapy significantly reduces the concentration of baclofen, ibuprofen, and/or bromethalin in canine whole blood over time.
Seven 500 mL bags of canine DEA 1.1 negative blood were divided into aliquots of 125 mL and randomly assigned to one of three treatment groups (baclofen, ibuprofen, bromethalin) or four control groups (a positive control for each treatment group and a negative control group).
Injectable ibuprofen (200 mg/kg), baclofen (8 mg/kg), or bromethalin (3 mg/kg) was apportioned into 125 mL aliquots of canine whole blood and incubated for 30 min at 38.5°C. ILE (12.4 mL, ) was added to each sample and the solution vortexed [215 rpm for 15 min at 37°C (98.6°F)]. Samples were obtained at designated time points (0, 15, 30, 60, 180, 360 min), centrifuged, and separated into serum and RBC fractions. Serum samples were ultracentrifuged (22,000 for 10 min at 37°C) to separate lipid rich and poor fractions. Samples were stored at -80°C prior to analysis.
A significant decrease in total drug concentration was established for bromethalin and its metabolite desmethylbromethalin compared to positive controls. ILE significantly reduced desmethylbromethalin at the 30-and 360-min time points. The remainder of the desmethylbromethalin time points did not reach significance. Bromethalin concentration was significantly reduced at all time points compared to positive controls. Neither baclofen nor ibuprofen had significant changes in concentration.
ILE therapy was effective at reducing the total drug concentration of bromethalin and its metabolite desmethylbromethalin supporting the lipid sink theory. As a single compartment study, this study does not evaluate other proposed mechanisms of action of ILE therapy. ILE therapy may have other means of significantly decreasing lipophilic drug concentration in cases of toxicosis.
确定静脉注射脂质乳剂(ILE)疗法是否会随着时间的推移显著降低犬全血中巴氯芬、布洛芬和/或溴敌隆的浓度。
将7袋500毫升犬DEA 1.1阴性血液分成125毫升的等分试样,并随机分配到三个治疗组(巴氯芬、布洛芬、溴敌隆)之一或四个对照组(每个治疗组一个阳性对照组和一个阴性对照组)。
将可注射的布洛芬(200毫克/千克)、巴氯芬(8毫克/千克)或溴敌隆(3毫克/千克)分配到125毫升犬全血等分试样中,并在38.5°C下孵育30分钟。向每个样品中加入ILE(12.4毫升, ),并将溶液涡旋[在37°C(98.6°F)下以215转/分钟的速度涡旋15分钟]。在指定时间点(0、15、30、60、180、360分钟)采集样品,离心并分离成血清和红细胞部分。血清样品进行超速离心(在37°C下以22,000 离心10分钟)以分离富含脂质和脂质贫乏的部分。样品在分析前保存在-80°C。
与阳性对照组相比,溴敌隆及其代谢物去甲基溴敌隆的总药物浓度显著降低。ILE在30分钟和360分钟时间点显著降低了去甲基溴敌隆的浓度。其余去甲基溴敌隆时间点未达到显著水平。与阳性对照组相比,溴敌隆浓度在所有时间点均显著降低。巴氯芬和布洛芬的浓度均无显著变化。
ILE疗法在降低溴敌隆及其代谢物去甲基溴敌隆的总药物浓度方面是有效的,支持脂质池理论。作为一项单室研究,本研究未评估ILE疗法的其他拟议作用机制。在中毒情况下,ILE疗法可能有其他显著降低亲脂性药物浓度的方法。