ENHANCEMENT OF ABSORPTION AND EFFECT OF GLIPIZIDE BY MAGNESIUM-HYDROXIDE

The effects of magnesium hydroxide on the pharmacokinetics and pharmacodynamics of glipizide were studied in eight healthy volunteers in a randomized crossover trial. After an overnight fast, 5 mg glipizide was given with either 150 ml water or water containing 850 mg magnesium hydroxide. Magnesium hydroxide increased the areas under the plasma glipizide concentration - time curves (AUC) from 0 to 1/2 hour and from 0 to 1 hour by 180% (p < 0.05) and 69% (p < 0.05), respectively. The peak plasma concentration, time to peak, total AUC, elimination half-life, and mean residence time of glipizide remained unchanged. The incremental plasma insulin area from 0 to 1/2 hour increased by 85% (p < 0.05), and the time to maximal insulin response was reduced (p < 0.05) during the magnesium hydroxide phase. The corresponding decremental plasma glucose area increased fourfold (p < 0.05), and the maximal glucose decrease was 35% greater (p < 0.05) than during the control phase. We conclude that the concomitant ingestion of magnesium hydroxide and glipizide may result in accelerated absorption of glipizide and increased early insulin and glucose responses.