Greater immediate gastric acid suppression with lansoprazole 30 mg administered as a 2-minute intravenous bolus injection versus a 30-minute infusion.
OBJECTIVE
To compare the pharmacokinetics, pharmacodynamics, and safety of lansoprazole administered as a 2-minute intravenous bolus injection versus a 30-minute continuous infusion.


METHODS
Phase I, open-label, randomized, crossover, single-center trial.


METHODS
Clinical research facility.


METHODS
Thirty-eight healthy volunteers aged 18-55 years.


METHODS
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.


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.


CONCLUSIONS
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.
Metz
David C
DC
Division of Gastroenterology, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. david.metz@uphs.upenn.edu
Devlin
John W
JW
Vakily
Majid
M
Atkinson
Stuart
S
Lloyd
Eric
E
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D005744:Gastric Acid; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D064747:Lansoprazole; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D053719:Tandem Mass Spectrometry
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064747:Lansoprazole