Plasma theophylline concentration and lung function in ponies with recurrent obstructive lung disease

Six ponies with recurrent obstructive lung disease were studied during two separate 60 min periods while receiving constant equal volume infusions of either aminophylline or sterile water. Dynamic lung compliance, pulmonary resistance, respiratory rate, tidal volume, blood gas tensions and heart rate were measured. Plasma samples were obtained for determination of theophylline concentrations before, and at 10 min intervals during, the infusion period. Excitability was assessed subjectively at these same time periods. The plasma theophylline concentrations in ponies were well predicted by a previously published model of theophylline pharmacokinetics in the horse. Sterile water had no effect on lung function. Aminophylline produced significant changes in lung function compared to baseline values, including a decrease in resistance at 30 min when the mean plasma theophylline concentration was 59 ± 14 μmol/litre and an increase in compliance at 60 mins at a mean plasma theophylline concentration of 102 ± 23 μmol/litre. Excitement was noted between 40 and 50 mins in all ponies (mean plasma theophylline concentration 74 ± 20 and 84 ±24 μmol/litre, respectively). Heart rate increased at 50 mins. The therapeutic range for intravenous (iv) theophylline concentration in ‘heavey’ ponies therefore appears to be between 59 and 84 μmol/litre when aminophylline is administered iv. Below 59 μmol/litre there was no consistent bronchodilator activity and above 84 μmol/litre excitement and tachycardia limited the usefulness of the drug.