Ingvast-Larsson C, Kallings P, Persson S, Appelgren L E, Wiese B
Swedish University of Agricultural Sciences, Faculty of Veterinary Medicine, Uppsala, Sweden.
J Vet Pharmacol Ther. 1989 Jun;12(2):189-99. doi: 10.1111/j.1365-2885.1989.tb00660.x.
The pharmacokinetics of theophylline at rest and the effects on cardio-respiratory and blood lactate responses to exercise were investigated after repeated oral administrations in six healthy Standardbred horses. A dose of 5 mg/kg body weight was administered every 12 h. The binding of theophylline to plasma protein was also determined. There was good agreement between predicted and observed plasma concentrations of theophylline at steady state. The mean half-life of elimination was shown to be 17.0 +/- 2.5 h, the mean half life of absorption was 1.6 +/- 1.8 h, the apparent volume of distribution was 852 +/- 99.0 ml/kg and total plasma clearance 0.61 +/- 0.08 ml/kg/min. Theophylline showed very low plasma protein binding (12%). The heart rate and blood lactate levels, during and after exercise, were significantly increased during theophylline-treatment. There was an increase of the arterial oxygen tension after exercise and the arterial carbon dioxide values before and after exercise were significantly lower than the premedication values. No severe adverse effects of the drug were noted. The recommended oral dose is therefore 5 mg/kg every 12 h but due to inter-individual variation, an adjustment of the dose may be necessary. The changes in the studied exercise parameters indicate that the performance capacity may be impaired by theophylline in the healthy horse.
在六匹健康的标准赛马中重复口服给药后，研究了静息状态下茶碱的药代动力学以及对运动时心肺和血乳酸反应的影响。每12小时给予5mg/kg体重的剂量。还测定了茶碱与血浆蛋白的结合情况。茶碱稳态时预测血浆浓度与实测血浆浓度之间具有良好的一致性。消除的平均半衰期显示为17.0±2.5小时，吸收的平均半衰期为1.6±1.8小时，表观分布容积为852±99.0ml/kg，血浆总清除率为0.61±0.08ml/kg/min。茶碱显示出非常低的血浆蛋白结合率（12%）。在茶碱治疗期间，运动期间和运动后的心率和血乳酸水平显著升高。运动后动脉血氧张力升高，运动前后的动脉二氧化碳值显著低于用药前值。未观察到该药物的严重不良反应。因此，推荐口服剂量为每12小时5mg/kg，但由于个体差异，可能需要调整剂量。所研究的运动参数的变化表明，茶碱可能会损害健康马匹的运动能力。
