University of Pennsylvania, School of Arts and Sciences, Philadelphia, PA 19104, USA,
Oregon State University, College of Pharmacy, Corvallis, OR 97331, USA.
J Zoo Wildl Med. 2021 Jan;51(4):905-914. doi: 10.1638/2020-0053.
Flunixin meglumine is the most commonly used nonsteroidal anti-inflammatory drug used to treat elephants; however, no pharmacokinetic study for flunixin has yet been conducted in these species, and dosages used range widely. Pharmacokinetic parameters of flunixin were determined in African () and Asian () elephants after single-dose oral administration of 0.8 and 1.5 mg/kg flunixin paste in each species. Elephant compliance to oral administration of banamine was occasionally challenging, especially among older, female African elephants. After administration of 0.8 mg/kg flunixin, mean serum concentrations peaked in approximately 1.3 hr at 2.1 ± 0.8 µg/ml for Asian ( = 8) and 2.8 hr at 2.5 ± 0.7 µg/ml for African ( = 8) elephants. Dosages of 1.5 mg/kg flunixin resulted in mean serum concentration peaks of 7.2 ± 1.5 µg/ml in Asian elephants ( = 7) and 4.4 ± 0.7 µg/ml in African elephants ( = 6). However, multiple-dose trials using 1.1 mg/kg flunixin resulted in peak serum concentrations that were again less in Asian than African elephants (2.7 µg/ml versus 4.4 µg/ml, respectively). Asian elephants consistently had lower time to maximal concentration, greater area under the curve, and longer mean residence times compared with African elephants. In other species, flunixin is excreted unchanged primarily via hepatic routes with small amounts in the urine. Asian elephants may engage in some level of enterohepatic recycling of flunixin, as was previously reported for phenylbutazone. This study supports that different oral dosing regimens should be used for Asian (1.0 mg/kg SID) and African (1.2 mg/kg SID) elephants, and oral administration techniques used should ensure complete dosage delivery.
氟尼辛葡甲胺是最常用于治疗大象的非甾体抗炎药；然而，尚未在这些物种中进行氟尼辛的药代动力学研究，并且使用的剂量范围很广。在每个物种中，给 0.8 和 1.5 mg/kg 的氟尼辛糊剂进行单次口服给药后，确定了非洲象（ ）和亚洲象（ ）中的氟尼辛药代动力学参数。口服 banamine 偶尔会对大象产生挑战，尤其是在年龄较大的雌性非洲象中。在给予 0.8 mg/kg 的氟尼辛后，亚洲象（ ）的血清浓度约在 1.3 小时时达到峰值，为 2.1 ± 0.8 µg/ml，而非洲象（ ）的血清浓度则在 2.8 小时时达到峰值，为 2.5 ± 0.7 µg/ml。给予 1.5 mg/kg 的氟尼辛，亚洲象（ ）的血清浓度峰值为 7.2 ± 1.5 µg/ml（ = 7），非洲象（ ）的血清浓度峰值为 4.4 ± 0.7 µg/ml（ = 6）。然而，使用 1.1 mg/kg 的氟尼辛进行多次剂量试验导致亚洲象的血清浓度峰值再次低于非洲象（分别为 2.7 µg/ml 与 4.4 µg/ml）。与非洲象相比，亚洲象的达峰时间更短、曲线下面积更大、平均停留时间更长。在其他物种中，氟尼辛主要通过肝脏途径以原形排泄，少量通过尿液排泄。亚洲象可能会进行一定程度的氟尼辛肠肝循环，这与以前报道的苯丁唑酮相似。本研究支持亚洲象（1.0 mg/kg SID）和非洲象（1.2 mg/kg SID）应使用不同的口服给药方案，并且应使用口服给药技术确保完全给予剂量。
