Laniesse Delphine, Guzman David Sanchez-Migallon, Knych Heather K, Smith Dale A, Mosley Cornelia, Paul-Murphy Joanne R, Beaufrère Hugues
Am J Vet Res. 2017 Jun;78(6):688-694. doi: 10.2460/ajvr.78.6.688.
OBJECTIVE To determine pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after SC administration to Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS 11 adult Hispaniolan Amazon parrots (6 males and 5 females; 11 to 27 years old). PROCEDURES A sterile formulation of butorphanol in P407 (But-P407) 25% (percentage determined as [weight of P407/weight of diluent] × 100]) was created (8.3 mg/mL). Five preliminary experiments (2 birds/experiment) were performed to determine the ideal dose for this species. The formulation then was administered (12.5 mg/kg, SC) to 8 birds. Blood samples were collected before (time 0) and 0.08, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Some birds were used more than once, with a washout period of ≥ 3 months between subsequent treatments. Butorphanol concentrations were quantitated by use of liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed by use of noncompartmental analysis. RESULTS Maximal plasma butorphanol concentration was reached at 1.31 hours. Plasma concentrations of butorphanol remained > 100 ng/mL for > 3 hours (all birds) or > 4 hours (5/8 birds) but < 8 hours (all birds). Half-life of the terminal slope was 3.41 hours. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE Butorphanol was absorbed well from the But-P407 25% by Hispaniolan Amazon parrots, and absorption followed a pharmacokinetic profile compatible with a sustained-release drug. A dose of 12.5 mg/kg, SC, would theoretically provide analgesia for 4 to 8 hours. No adverse effects were detected. Studies on the pharmacodynamics of this formulation are necessary to confirm the degree and duration of analgesia.
目的 确定对伊斯帕尼奥拉亚马逊鹦鹉(Amazona ventralis)皮下注射掺入泊洛沙姆407(P407)的酒石酸布托啡诺后的药代动力学。动物 11只成年伊斯帕尼奥拉亚马逊鹦鹉(6只雄性和5只雌性;11至27岁)。方法 制备含25%(百分比定义为[P407重量/稀释剂重量]×100%)P407的酒石酸布托啡诺无菌制剂(But-P407)(8.3 mg/mL)。进行了5项预实验(每项实验2只鸟)以确定该物种的理想剂量。然后将该制剂(12.5 mg/kg,皮下注射)给予8只鸟。在给药前(时间0)以及给药后0.08、0.5、1、2、4、8、12和24小时采集血样。一些鸟被多次使用,后续治疗之间的洗脱期≥3个月。使用液相色谱-串联质谱法定量酒石酸布托啡诺浓度。采用非房室分析法进行药代动力学分析。结果 最大血浆酒石酸布托啡诺浓度在1.31小时达到。酒石酸布托啡诺的血浆浓度在>3小时(所有鸟)或>4小时(5/8只鸟)内保持>100 ng/mL,但<8小时(所有鸟)。末端斜率的半衰期为3.41小时。未检测到不良反应。结论及临床意义 伊斯帕尼奥拉亚马逊鹦鹉对25%的But-P407中的酒石酸布托啡诺吸收良好,且吸收遵循与缓释药物相符的药代动力学特征。理论上,12.5 mg/kg皮下注射剂量可提供4至8小时的镇痛效果。未检测到不良反应。有必要对该制剂的药效学进行研究以确认镇痛程度和持续时间。