Pharmacokinetics and pharmacodynamics of buprenorphine and sustained-release buprenorphine after administration to adult alpacas
Pharmacokinetics and pharmacodynamics of buprenorphine and sustained-release buprenorphine after administration to adult alpacas
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DOI：
10.2460/ajvr.78.3.321
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发表时间：
2017-03-01
影响因子：
1
通讯作者：
Hubbell, John A. E.
中科院分区：
文献类型：
--
作者：
Dooley, S. Bryce;Aarnes, Turi K.;Hubbell, John A. E.
目的 确定成年羊驼静脉注射和皮下注射后丁丙诺啡的药代动力学和药效学以及皮下注射后缓释（SR）丁丙诺啡的药代动力学和药效学。 动物 6 只羊驼。 程序 对每只羊驼注射丁丙诺啡（0.02 mg/kg，IV 和 SC）和 SR 丁丙诺啡（0.12 mg/kg，SC），为期 14 天。给药之间的清除期。在 96 小时内收集了 21 份静脉血样本，用于测定丁丙诺啡的血浆浓度。通过使用非房室分析计算药代动力学参数。通过镇静、心率和呼吸频率以及热和机械抗伤害指数来评估药效学参数。结果静脉注射和皮下注射丁丙诺啡后的平均+/-SD最大浓度分别为11.60+/-4.50ng/mL和1.95+/-0.80ng/mL。平均清除率为 3.00 +/- 0.33 L/h/kg，IV 给药后稳态分布容积为 3.8 +/- 1.0 L/kg。 IV和SC给药后的终末消除半衰期分别为1.0+/-0.2小时和2.7+/-2.8小时。 IV和SC给药后平均停留时间分别为1.3+/-0.3小时和3.6+/-3.7小时。生物利用度为 64 +/- 28%。皮下注射 SR 丁丙诺啡后，4 只羊驼样本中的血浆浓度低于 LLOQ。丁丙诺啡给药后药效学参数没有显着变化。羊驼在所有治疗后表现出轻微的行为变化。结论和临床相关性对健康羊驼施用丁丙诺啡导致中等生物利用度、快速清除和短半衰期。 SC 注射 SR 丁丙诺啡后，仅 2 只羊驼体内可检测到血浆浓度。
OBJECTIVE To determine pharmacokinetics and pharmacodynamics of buprenorphine after IV and SC administration and of sustained-release (SR) buprenorphine after SC administration to adult alpacas.ANIMALS 6 alpacas.PROCEDURES Buprenorphine (0.02 mg/kg, IV and SC) and SR buprenorphine (0.12 mg/kg, SC) were administered to each alpaca, with a 14-day washout period between administrations. Twenty-one venous blood samples were collected over 96 hours and used to determine plasma concentrations of buprenorphine. Pharmacokinetic parameters were calculated by use of noncompartmental analysis. Pharmacodynamic parameters were assessed via sedation, heart and respiratory rates, and thermal and mechanical antinociception indices.RESULTS Mean +/- SD maximum concentration after IV and SC administration of buprenorphine were 11.60 +/- 4.50 ng/mL and 1.95 +/- 0.80 ng/mL, respectively. Mean clearance was 3.00 +/- 0.33 L/h/kg, and steady-state volume of distribution after IV administration was 3.8 +/- 1.0 L/kg. Terminal elimination half-life was 1.0 +/- 0.2 hours and 2.7 +/- 2.8 hours after IV and SC administration, respectively. Mean residence time was 1.3 +/- 0.3 hours and 3.6 +/- 3.7 hours after IV and SC administration, respectively. Bioavailability was 64 +/- 28%. Plasma concentrations after SC administration of SR buprenorphine were below the LLOQ in samples from 4 alpacas. There were no significant changes in pharmacodynamic parameters after buprenorphine administration. Alpacas exhibited mild behavioral changes after all treatments.CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine administration to healthy alpacas resulted in moderate bioavailability, rapid clearance, and a short half-life. Plasma concentrations were detectable in only 2 alpacas after SC administration of SR buprenorphine.