THE EFFECTS OF MAGNESIUM-HYDROXIDE ON THE ABSORPTION AND EFFICACY OF 2 GLIBENCLAMIDE PREPARATIONS

1 The effect of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations was investigated in healthy volunteers in two separate studies, using a randomized cross-over design with two phases. 2 A single dose of magnesium hydroxide (850 mg) or water only (150 ml) was given immediately after the ingestion of a micronised (1.75 mg, seven subjects) or a nonmicronised (2.5 mg, six subjects) preparation of glibenclamide. Plasma concentrations of glibenclamide, insulin and glucose were measured. 3 Magnesium hydroxide accelerated (P < 0.05) the absorption of glibenclamide from the micronised preparation to a small extent but the extent of absorption and the insulin and glucose responses were unaltered. 4 Coadministration of magnesium hydroxide with the non-micronised glibenclamide preparation increased the area under the plasma glibenclamide concentration-time curve from 0 to 3 h, five-fold (P < 0.05), the total area three-fold (P < 0.05) and the peak drug concentration three-fold (P < 0.05). The incremental insulin area from 0 to 3 h was increased 35-fold (P < 0.05) and the maximum insulin response 10-fold (P < 0.05) by magnesium hydroxide. 5 Concomitant ingestion of magnesium hydroxide and non-micronised glibenclamide may greatly enhance the absorption and efficacy of glibenclamide. The absorption of micronised glibenclamide appears to be only slightly influenced by magnesium hydroxide.