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The disposition characteristics of theophylline from two sustained release formulations (Theolong and Theodur) administered orally at the dose of 100 mg/head were compared in two groups of nonanesthetized dogs following a 24-hr period of starvation (fasting) and immediately after feeding (nonfasting). The pharmacokinetics of the two sustained release theophylline preparations could be analyzed by a two-compartment open model. The peak plasma concentration, area under the curve and bioavailability of theophylline in Theolong in the fasting group were significantly higher the respective parameters in the nonfasting group, suggesting a decrease in the absorption process. In contrast, there were no significant differences in these parameters in Theodur between both the groups. The increase in urinary flow rate induced by Theolong was significantly lower in the nonfasting group. In both the groups, two metabolites of theophylline were isolated from the urine and identified as 3-methylxanthine and 1,3-dimethyluric acid by HPLC. When the animals were administered Theolong after feeding the cumulative urinary excretion of theophylline and its metabolites was about 50% lower than that after fasting medication. These results suggest that effects of food intake on the absorption of theophylline in dogs are different depending on the sustained release formulations.

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Effects of food intake on the pharmacokinetics, metabolism and urinary excretion of two sustained release theophylline preparations in nonanesthetized dogs.