Wong D M, Davis J L, Alcott C J, Hepworth-Warren K L, Galow-Kersh N L, Rice S, Coetzee J F
Department of Veterinary Clinical Sciences, Lloyd Veterinary Medical Center, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
J Vet Pharmacol Ther. 2015 Jun;38(3):301-4. doi: 10.1111/jvp.12192. Epub 2014 Nov 27.
The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0-∞ ) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1-12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.
本研究的目的是评估马匹单次口服阿普唑仑的药代动力学特性和生理效应。七匹成年雌性马接受了剂量为0.04 mg/kg体重的阿普唑仑口服给药。在不同时间点采集血样，使用液相色谱/质谱法测定阿普唑仑及其代谢物α-羟基阿普唑仑。采用单室模型分析阿普唑仑的药代动力学特征。单次给药阿普唑仑后的平均血浆药代动力学参数（±标准差）如下：Cmax为14.76±3.72 ng/mL，曲线下面积（AUC0-∞）为358.77±76.26 ng·h/mL。中位（范围）达峰时间（Tmax）为3小时（1 - 12小时）。每匹马均检测到α-羟基阿普唑仑浓度，尽管浓度较低（Cmax为1.36±0.28 ng/mL）。每12小时进行重复体格检查以及评估镇静和共济失调程度，以评估不良反应。阿普唑仑口服片剂在成年马中被吸收，未观察到临床相关不良事件。有必要进一步评估阿普唑仑对马匹重复给药的情况及其给药安全性。
