Plasma concentrations, bioavailability and dissolution of chlorpropamide.

The bioavailability of chlorpropamide from two new formulations (Melitase tablets) has been compared to that from a reference formulation which is currently in clinical use as a hypoglycaemic agent. In both rate and extent of bioavailability, all three formulations may be considered equivalent, providing allowances are made for differences in drug content. With 95% confidence, the mean bioavailability of chlorpropamide from the new formulations was within about 16% of the mean from the reference formulaion, and formulation-related differences were not statistically significant. Although all three formulations were shown to have similar dissolution profiles, dissolution of chlorpropamide was pH-dependent in vitro. Dissolution was almost complete during 30 min at pH 7.2, but only 40%-60% had dissolved during 90 min at pH 2.0. A peak mean concentration of 22.7 mug/ml was reached 3 h after administration of 2 x 100 mg tablets of the new formulation and peak mean concentrations of 26.8 mug/ml and 27.4 mug/ml were reached 3 h and 4 hours after administration of one 250 mg tablet of the new formulation and one 250 mg tablet of the reference formulation respectively. Formulation-related differences of mean plasma concentrations (after scaling for equal doses of 250mg) were not significant and each formulation provided similar plasma concentrations at corresponding times after administration. Statistically significant subject-related differences in all the parameters of bioavailability were shown by analyses of variance.