Acute and subacute toxicities of theophylline are directly reflected by its plasma concentration in dogs

Abstract

The purpose of this study was to evaluate the relationship between acute and subacute toxicity and blood levels of theophylline in dogs. Theophylline was administered intravenously into dogs once (at doses of 50, 100 and 150 mg/kg) or for 4 weeks (at doses of 20, 35 and 70 mg/kg/day). In the single dose toxicity study, by increasing the dose of theophylline, plasma concentration increased and the severity of toxic symptoms were intensified. After a single dosing of theophylline, accentuated heart rate and vomiting were observed at a concentration of more than 67 micrograms/ml, and excitement, spasm and hyperpnea were observed at more than 130 micrograms/ml. Animals died after tonic convulsion at 180 micrograms/ml. In the repeated dose toxicity study, the plasma concentration of theophylline increased dependent on dosage, and was not affected by repeated dosing. Even under these conditions, the toxic symptoms were quite similar to those of the single dose, except for an additional decrease in movement, body weight reduction and myocardial lesion. These present results suggest that the severity of theophylline toxicity is dependent on its plasma concentrations rather than accumulated dosages. The blood concentration of theophylline-treated patients should be maintained within the therapeutic range in order to diminish risk.