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 less than 0.05) and 69% (p less than 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 less than 0.05), and the time to maximal insulin response was reduced (p less than 0.05) during the magnesium hydroxide phase. The corresponding decremental plasma glucose area increased fourfold (p less than 0.05), and the maximal glucose decrease was 35% greater (p less than 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.