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酒石酸布托啡诺在长效泊洛沙姆407凝胶制剂中给伊斯帕尼奥拉亚马逊鹦鹉(Amazona ventralis)用药后的药代动力学。

Pharmacokinetics of butorphanol tartrate in a long-acting poloxamer 407 gel formulation administered to Hispaniolan Amazon parrots (Amazona ventralis).

作者信息

Laniesse Delphine, Guzman David Sanchez-Migallon, Knych Heather K, Smith Dale A, Mosley Cornelia, Paul-Murphy Joanne R, Beaufrère Hugues

出版信息

Am J Vet Res. 2017 Jun;78(6):688-694. doi: 10.2460/ajvr.78.6.688.

Abstract

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.

摘要

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。

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