Dose–response evaluation of the antisecretory effect of continuous infusion intravenous lansoprazole regimens over 48 h

Summary Background  Attainment of intragastric pH < 6.0 may require high‐dose continuously infused proton pump therapy. Aim  To assess the pharmacokinetic and pharmacodynamic dose–responses of continuous infusion regimens of lansoprazole. Methods  Healthy adult subjects were assigned to lansoprazole 60‐mg intravenous bolus, followed by 6‐mg/h continuous infusion; a 90‐mg intravenous bolus followed by 6‐, 7.5‐, or 9‐mg/h continuous infusion; or placebo. Results  Mean intragastric pH values for lansoprazole regimens ranged from 4.8 to 5.2 (0–24 h), 5.5 to 6.0 (>24 to 48 h) and 5.2 to 5.6 (0–48 h). Within these three intervals, the percentages of time intragastric pH exceeded 4, 5 and 6 ranged from 65% to 96%, 54% to 88% and 30% to 61% respectively. Pharmacokinetic parameters were dose‐independent with steady‐state plasma concentrations achieved within 6–12 h postdose and maintained over 48 h. The mean systemic clearance of lansoprazole was lower in CYP2C19 heterozygous metabolizers than in homozygous extensive metabolizers (9.2 vs. 16.5 L/h), with substantial variability resulting in overlapping ranges of clearance values for both subpopulations. All lansoprazole regimens were well‐tolerated. Conclusions  Lansoprazole administered as a 60‐mg intravenous bolus followed by 6‐mg/h continuous infusion produced intragastric pH effects comparable with those of higher dosage regimens.