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Dose-response evaluation of the antisecretory effect of continuous infusion intravenous lansoprazole regimens over 48
1Division of Gastroenterology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. c-howden@northwestern.edu
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.
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