Guzman David Sanchez-Migallon, Flammer Keven, Paul-Murphy Joanne R, Barker Steven A, Tully Thomas N
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Dr, Baton Rouge, LA 70803-8410, USA.
J Avian Med Surg. 2011 Sep;25(3):185-91. doi: 10.1647/2009-054.1.
Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (< 10%), thus precluding the use of this route of administration for clinical purposes. Based on these results, in Hispaniolan Amazon parrots, butorphanol tartrate dosed at 5 mg/kg IV or IM would have to be administered every 2 and 3 hours, respectively, to maintain plasma concentrations consistent with published therapeutic levels. To our knowledge, this is the first published study presenting the pharmacokinetic analysis of butorphanol tartrate in a psittacine species as well as the first study presenting pharmacokinetic analysis of butorphanol after oral administration in any avian species.
以往的研究已证实，具有κ-阿片受体亲和力的阿片类药物在鸟类疼痛管理中的临床应用是有效的。布托啡诺是一种κ-阿片受体激动剂和μ-阿片受体拮抗剂，目前被许多临床医生认为是用于此用途的首选阿片类药物。然而，尽管有研究报道了布托啡诺在鹦鹉中的镇痛特性，但尚未确定任何鹦鹉物种的给药间隔。本研究在伊斯帕尼奥拉亚马逊鹦鹉（Amazona ventralis）中的目标是评估静脉注射（IV）、肌肉注射（IM）和口服（PO）酒石酸布托啡诺后的药代动力学，并确定口服给药后酒石酸布托啡诺的生物利用度。本研究使用了12只伊斯帕尼奥拉亚马逊鹦鹉，采用完全交叉实验设计，研究的每个部分间隔3个月。在每个阶段，将鸟类随机分为3组（n = 4）。在IV、IM和PO研究中，分别以5 mg/kg的剂量在贵要静脉或胸肌中注射一次酒石酸布托啡诺，或以口服溶液通过饲管注入嗉囊中。给予布托啡诺后，在IV和IM研究中，于1、5、15、30、60、90、120、180和240分钟采集血样；在PO研究中，于5、15、30、60、90、120、180、240和300分钟采集血样。由于鸟类体型限制，使用原始数据点合并来生成每个时间点的平均血浆布托啡诺浓度。对于每项研究，每组（n = 4）的鸟类在给药后采血3次。通过高效液相色谱/串联质谱法测定血浆布托啡诺浓度，并计算药代动力学参数。发现酒石酸布托啡诺在IM给药后具有高生物利用度和快速消除的特点。相比之下，口服给药导致生物利用度低（<10%），因此排除了将该给药途径用于临床目的的可能性。基于这些结果，在伊斯帕尼奥拉亚马逊鹦鹉中，分别每2小时和3小时静脉注射或肌肉注射5 mg/kg的酒石酸布托啡诺，以维持与已发表的治疗水平一致的血浆浓度。据我们所知，这是首次发表的关于酒石酸布托啡诺在鹦鹉物种中的药代动力学分析的研究，也是首次发表的关于任何鸟类物种口服布托啡诺后的药代动力学分析的研究。
