Pharmacokinetics of Salbutamol in Thoroughbred Horses After a Single Intravenous or Inhaled Administration.

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2024-11-11 DOI:10.1111/jvp.13491
Motoi Nomura, Taisuke Kuroda, Minoru Ohta, Kanichi Kusano, Yohei Minamijima, Shunichi Nagata
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Abstract

Salbutamol is a short-acting and selective beta-2 adrenergic agonist. Inhaled (IH) administration of salbutamol is widely used to control lower respiratory tract disease in horses. Here, we estimated the pharmacokinetic parameters of salbutamol after a single intravenous (IV) or IH administration in six horses, and we statistically analysed the detection times with various dosing regimens. Plasma and urine concentrations of salbutamol were measured by liquid chromatography-tandem mass spectrometry, and data were modelled by using a nonlinear mixed effect model followed by Monte Carlo simulation (MCS). With IH salbutamol, the maximum plasma concentration was 0.12 ± 0.06 ng/mL at 0.29 ± 0.17 h after administration. Typical values were, for clearance, 1.53 L/kg/h; distribution volume at steady state, 5.43 L/kg; terminal half-life, 6.06 h; IH bioavailability, 19.0%; and urine to plasma ratio, 2057. Statistically estimated 95th percentile detection times in the urine at levels below the international screening limit (0.5 ng/mL) proposed by the International Federation of Horseracing Authorities, as simulated in 5000 horses by MCS, were 44 h after 1.6 μg/kg q 24 and 54 h after 1.6 μg/kg q 4 h over a 3-day IH administration period.

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沙丁胺醇在纯血马体内单次静脉注射或吸入后的药代动力学。
沙丁胺醇是一种短效和选择性β-2肾上腺素能激动剂。沙丁胺醇吸入(IH)给药被广泛用于控制马的下呼吸道疾病。在此,我们估算了六匹马单次静脉注射(IV)或吸入给药后沙丁胺醇的药代动力学参数,并对不同给药方案的检测时间进行了统计分析。通过液相色谱-串联质谱法测量了沙丁胺醇的血浆和尿液浓度,并使用非线性混合效应模型和蒙特卡罗模拟(MCS)对数据进行了建模。对于 IH 沙丁胺醇,给药后 0.29 ± 0.17 h 的最大血浆浓度为 0.12 ± 0.06 ng/mL。典型值为:清除率为 1.53 升/千克/小时;稳态分布容积为 5.43 升/千克;终末半衰期为 6.06 小时;IH 生物利用率为 19.0%;尿液与血浆比率为 2057。通过 MCS 对 5000 匹马进行模拟,在 3 天的 IH 给药期内,尿液中低于国际赛马联合会提出的国际筛查限(0.5 纳克/毫升)水平的第 95 百分位数检测时间分别为:1.6 μg/kg q 24 小时后 44 小时和 1.6 μg/kg q 4 小时后 54 小时。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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The Single-Dose Pharmacokinetics of a Compounded Levetiracetam Formulation and Bioequivalence to a Commercial Formulation in Healthy Dogs. Antimicrobial Pharmacokinetic Studies in Sea Turtles: A Review. Issue Information Pharmacokinetics of Salbutamol in Thoroughbred Horses After a Single Intravenous or Inhaled Administration. Comparative Pharmacokinetics of Intravenous and Subcutaneous Omeprazole in Sheep and Goats.
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