The effects of sodium bicarbonate and aluminium hydroxide on the absorption and activity of glipizide have been studied in healthy volunteers in two randomized cross-over trials. After an overnight fast, 5 mg glipizide was given either with 150 ml water or with water containing 3.0 g sodium bicarbonate or 1.0 g aluminium hydroxide. Sodium bicarbonate significantly increased the AUC of plasma glipizide from 0 to 0.5 h, 0 to 1 h, and from 0 to 2 h (six-, four- and twofold, respectively). The time to peak concentration (tmax) fell from 2.5 h during the control phase to 1.0 h during the sodium bicarbonate phase. The absorption half-life (t1/2a), lag time and mean residence time (MRT) were also significantly decreased. No significant change in peak plasma concentration (Cmax), total AUC or elimination half-life (t1/2) was noted. The decremental plasma glucose areas from 0 to 1 h and 0 to 2 h were significantly larger (80% and 50%, respectively) than during the control phase. The maximal decrease in glucose was 50% greater during the sodium bicarbonate phase, and the time to reach it was reduced by 35 min. Aluminium hydroxide had no significant effects on the rate or extent of absorption of glipizide, and the glucose response also remained unaffected. It is concluded that the concomitant ingestion of sodium bicarbonate and glipizide may result in accelerated absorption of glipizide and an increased effect on glucose. A common dose of aluminium hydroxide did not appear to affect the absorption of glipizide.