Pharmacokinetics and cardio‐respiratory effects of oral theophylline in exercised horses

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Abstract
The pharmacokinetics of theophylline at rest and the effects on cardiorespiratory 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 apparant 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 arterual 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.

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