STUDY OBJECTIVE To compare the pharmacokinetics, pharmacodynamics, and safety of lansoprazole administered as a 2-minute intravenous bolus injection versus a 30-minute continuous infusion. DESIGN Phase I, open-label, randomized, crossover, single-center trial. SETTING Clinical research facility. SUBJECTS Thirty-eight healthy volunteers aged 18-55 years. INTERVENTION Each subject received one of three regimens. Each regimen contained the same three treatments but in a different sequence: an intravenous injection of lansoprazole 30 mg/10 ml of normal saline over 2 minutes, an infusion of lansoprazole 30 mg/60 ml of normal saline over 30 minutes, and an intravenous injection of 10 ml of normal saline (placebo) over 2 minutes. Each treatment was administered once/day for 7 days, with a washout period of at least 5 days separating each one. MEASUREMENTS AND MAIN RESULTS Blood samples were assayed for lansoprazole concentrations by using liquid chromatography with tandem mass spectrometry. After the 2-minute administration, mean peak lansoprazole concentrations were about 2-fold higher than those after the 30-minute administration on days 1 and 7. Lansoprazole area under the concentration versus time curve met criteria for bioequivalence on both days. Two-minute administration resulted in a greater percentage of time that the 24-hour pH was above 4 compared with the 30-minute administration (53% vs 47%, p=0.045), with comparable 24-hour integrated gastric acidity (114.4 vs 91.6 mmol*hr/L for 2-min vs 30-min, p=0.335). Significantly greater acid suppression occurred during the first hour after the 2-minute administration compared with that after the 30-minute administration (p < or = 0.001). Safety profiles were similar among the regimens. CONCLUSION Greater immediate gastric acid suppression occurred after administration of lansoprazole 30 mg over 2 minutes than over 30 minutes, with other pharmacokinetic, pharmacodynamic, and safety profiles being similar.