Bioavailability of Theodel, a new theophylline tablet, in humans

Abstract

The bioavailability of Theodel, a new scored tablet of theophylline, was investigated in eight healthy adult volunteers. Rate of absorption and AUC infinity were compared after single oral doses of Theodel (250 mg), of an aqueous solution (250 mg), and of two Theolair tablets (2 X 125 mg). Theophylline was rapidly absorbed from the Theodel tablet, with a t1/2abs of 0.44 +/- 0.37 h; maximum plasma concentrations of 8.0 +/- 2.3 mg/l were reached after 1.8 +/- 0.8 h. Almost the entire dose was recovered from urine as theophylline and its major metabolites, 1,3-dimethyluric acid, 1-methyluric acid, and 3-methylxanthine. Theophylline was, therefore, efficiently absorbed from this formulation. The plasma elimination half-life ranged from 5.9 to 10.4 h. Based on the assumption that absorption is complete, the plasma clearance ranged from 0.028 to 0.048 1 X h-1 X kg-1, and the apparent volume of distribution from 0.38 to 0.57 1/kg. No significant difference between the rate and the extent of theophylline absorption was observed for the three preparations, which are thus bioequivalent. Simulations of plasma levels after repeated administration of Theodel tablets showed that plasma theophylline concentrations remain in the therapeutic range with three doses per day.