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布托啡诺和缓释布托啡诺在成年羊驼给药后的药代动力学和药效学

Pharmacokinetics and pharmacodynamics of buprenorphine and sustained-release buprenorphine after administration to adult alpacas.

作者信息

Dooley S Bryce, Aarnes Turi K, Lakritz Jeffrey, Lerche Phillip, Bednarski Richard M, Hubbell John A E

出版信息

Am J Vet Res. 2017 Mar;78(3):321-329. doi: 10.2460/ajvr.78.3.321.

Abstract

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 ± l.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.

摘要

目的 确定成年羊驼静脉注射(IV)和皮下注射(SC)丁丙诺啡后以及皮下注射缓释(SR)丁丙诺啡后的药代动力学和药效学。动物 6 只羊驼。方法 给每只羊驼分别静脉注射和皮下注射丁丙诺啡(0.02 mg/kg)以及皮下注射 SR 丁丙诺啡(0.12 mg/kg),给药间隔为 14 天清洗期。在 96 小时内采集 21 份静脉血样,用于测定丁丙诺啡的血浆浓度。采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性抗伤害感受指数评估药效学参数。结果 静脉注射和皮下注射丁丙诺啡后的平均±标准差最大浓度分别为 11.60±4.50 ng/mL 和 1.95±0.80 ng/mL。平均清除率为 3.00±0.33 L/h/kg,静脉注射后的稳态分布容积为 3.8±1.0 L/kg。静脉注射和皮下注射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。静脉注射和皮下注射后的平均驻留时间分别为 1.3±0.3 小时和 3.6±3.7 小时。生物利用度为 64±28%。4 只羊驼皮下注射 SR 丁丙诺啡后的血浆浓度低于最低定量限(LLOQ)。丁丙诺啡给药后药效学参数无显著变化。所有治疗后羊驼均表现出轻度行为改变。结论及临床意义 给健康羊驼注射丁丙诺啡导致中等生物利用度、快速清除和较短半衰期。皮下注射 SR 丁丙诺啡后仅在 2 只羊驼中可检测到血浆浓度。

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