Ditheophylline succinate: transfer of theophylline across everted rat intestinal sacs.
The cumulative theophylline transfer rate across 10-cm everted rat intestinal sacs incubated at 37 degrees in pH 7.4 Krebs phosphate buffer was determined. A suspension of ditheophylline succinate ( a potential prodrug of theophylline) and a solution of theophylline at equimolar concentration were evaluated to determine the magnitude of the difference between the cumulative theophylline transfer rates from the two preparations. A linear concentration dependency for the rate across the intestinal wall was evidenced. The theophylline formation rate from ditheophylline succinate suspended in pH 7.4 Krebs buffer at 37 degrees followed apparent zero-order kinetics. The observed difference (fourfold) between the cumulative transfer rates estimated for the theophylline solution and the ditheophylline succinate suspention was attributed to the prevailing theophylline concentration in the mucosal solutions. The biopharmaceutical implication of these observations are discussed.
Ditheophylline succinate: transfer of theophylline across everted rat intestinal sacs. The cumulative theophylline transfer rate across 10-cm everted rat intestinal sacs incubated at 37 degrees in pH 7.4 Krebs phosphate buffer was determined. A suspension of ditheophylline succinate ( a potential prodrug of theophylline) and a solution of theophylline at equimolar concentration were evaluated to determine the magnitude of the difference between the cumulative theophylline transfer rates from the two preparations. A linear concentration dependency for the rate across the intestinal wall was evidenced. The theophylline formation rate from ditheophylline succinate suspended in pH 7.4 Krebs buffer at 37 degrees followed apparent zero-order kinetics. The observed difference (fourfold) between the cumulative transfer rates estimated for the theophylline solution and the ditheophylline succinate suspention was attributed to the prevailing theophylline concentration in the mucosal solutions. The biopharmaceutical implication of these observations are discussed.