Comparator PH Study to Evaluate the Single-dose Pharmacodynamics of Dual Delayed-release Dexlansoprazole 60 Mg and Delayed-release Esomeprazole 40 Mg

Overview

Journal Clin Exp Gastroenterol

Publisher Dove Medical Press

Specialty Gastroenterology

Date 2011 Oct 22

PMID 22016582

Citations 19

Authors

Michael Kukulka

Corey Eisenberg

Sai Nudurupati

Affiliations

Soon will be listed here.

Abstract

Background: This paper describes a Phase 1, single-center, randomized, open-label, two-period crossover study which compared the pharmacodynamic effects of single doses of dexlansoprazole modified-release 60 mg and esomeprazole 40 mg on 24-hour intragastric pH in healthy adult subjects.

Methods: Forty-four subjects aged 20-54 years were randomized in a 1:1 ratio to two sequence groups defining the order in which they received dexlansoprazole and esomeprazole in periods 1 and 2. Primary pharmacodynamic end points over 24 hours postdose were percentage of time with intragastric pH > 4 and mean pH, and secondary pharmacodynamic end points were percentage of time intragastric pH > 4, and mean pH at 0-12 hours, and at >12-24 hours postdose. Each drug was given after an overnight fast and one hour before breakfast. Continuous pH recording began immediately before dosing through to 24 hours postdose.

Results: At 0-24 hours postdose, the mean percentage of time with pH > 4 for dexlansoprazole and esomeprazole was 58% and 48%, respectively; the difference was statistically significant (P = 0.003). The average of mean pH values at 0-24 hours postdose for dexlansoprazole and esomeprazole were 4.3 and 3.7, respectively; the difference was statistically significant (P < 0.001). At >12-24 hours postdose, mean percentage of time with pH > 4 and average of mean pH were greater for dexlansoprazole (60% and 4.5, respectively) compared with esomeprazole (42% and 3.5, respectively); the difference was statistically significant (P < 0.001 for both intervals). At 0-12 hours postdose, the difference in dexlansoprazole and esomeprazole values for the pharmacodynamic end points was not statistically significant.

Conclusion: For the entire 24-hour postdose period, predominantly resulting from the >12-24-hour postdose interval, the average intragastric pH following a single dose of dexlansoprazole 60 mg was higher compared with that observed following a single dose of esomeprazole 40 mg, and the difference was statistically significant.

Citing Articles

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Jalihal U, Mahapatra J, Kumar A, Bharadwaj T, Singh H, Mehta V Cureus. 2024; 16(10):e71418.

PMID: 39539895 PMC: 11558283. DOI: 10.7759/cureus.71418.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

Lim H, Park J, Chung H, Lee S, Park J, Park J BMC Gastroenterol. 2023; 23(1):447.

PMID: 38110901 PMC: 10729464. DOI: 10.1186/s12876-023-03087-6.

Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study.

Han S, Choi H, Kim Y, Choi S, Kim S, Nam J Gut Liver. 2022; 17(1):92-99.

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Comparative analysis of the effect of PO administered acid suppressants on gastric pH in healthy cats.

Ryan P, Odunayo A, Price J, Hecht S, Hillsman S, Galyon G J Vet Intern Med. 2020; 34(5):1879-1885.

PMID: 32885499 PMC: 7517516. DOI: 10.1111/jvim.15887.

A comparison between dexlansoprazole modified release-based and lansoprazole-based nonbismuth quadruple (concomitant) therapy for first-line eradication: a prospective randomized trial.

Tai W, Liang C, Bi K, Kuo C, Lu L, Wu C Infect Drug Resist. 2019; 12:2923-2931.

PMID: 31571945 PMC: 6754331. DOI: 10.2147/IDR.S213998.

References

Katz P, Ginsberg G, Hoyle P, Sostek M, Monyak J, Silberg D . Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis. Aliment Pharmacol Ther. 2007; 25(5):617-28. DOI: 10.1111/j.1365-2036.2006.03235.x. View

Junghard O, Hassan-Alin M, Hasselgren G . The effect of the area under the plasma concentration vs time curve and the maximum plasma concentration of esomeprazole on intragastric pH. Eur J Clin Pharmacol. 2002; 58(7):453-8. DOI: 10.1007/s00228-002-0502-1. View

DeVault K, Talley N . Insights into the future of gastric acid suppression. Nat Rev Gastroenterol Hepatol. 2009; 6(9):524-32. DOI: 10.1038/nrgastro.2009.125. View

Warrington S, Baisley K, Dunn K, Boyce M, Morocutti A . Effects of single doses of rabeprazole 20 mg and esomeprazole 40 mg on 24-h intragastric pH in healthy subjects. Eur J Clin Pharmacol. 2006; 62(9):685-91. DOI: 10.1007/s00228-006-0148-5. View

Hassan-Alin M, Andersson T, Bredberg E, Rohss K . Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects. Eur J Clin Pharmacol. 2001; 56(9-10):665-70. DOI: 10.1007/s002280000206. View

Miner Jr P, Tutuian R, Castell D, Liu S, Sostek M . Intragastric acidity after switching from 5-day treatment with intravenous pantoprazole 40 mg/d to 5-day treatment with oral esomeprazole 40 mg/d or pantoprazole 40 mg/d: an open-label crossover study in healthy adult volunteers. Clin Ther. 2006; 28(5):725-33. DOI: 10.1016/j.clinthera.2006.05.001. View

Vakily M, Zhang W, Wu J, Atkinson S, Mulford D . Pharmacokinetics and pharmacodynamics of a known active PPI with a novel Dual Delayed Release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin. 2009; 25(3):627-38. DOI: 10.1185/03007990802693883. View

Bladh N, Blychert E, Johansson K, Backlund A, Lundin C, Niazi M . A new esomeprazole packet (sachet) formulation for suspension: in vitro characteristics and comparative pharmacokinetics versus intact capsules/tablets in healthy volunteers. Clin Ther. 2007; 29(4):640-9. DOI: 10.1016/j.clinthera.2007.03.014. View

Armstrong D . Review article: gastric pH -- the most relevant predictor of benefit in reflux disease?. Aliment Pharmacol Ther. 2004; 20 Suppl 5:19-26. DOI: 10.1111/j.1365-2036.2004.02140.x. View

10.

Hunfeld N, Touw D, Mathot R, Mulder P, van Schaik R, Kuipers E . A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism. Aliment Pharmacol Ther. 2009; 31(1):150-9. DOI: 10.1111/j.1365-2036.2009.04150.x. View

11.

Miner Jr P, Katz P, Chen Y, Sostek M . Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study. Am J Gastroenterol. 2003; 98(12):2616-20. DOI: 10.1111/j.1572-0241.2003.08783.x. View

12.

Thoring M, Hedenstrom H, Eriksson L . Rapid effect of lansoprazole on intragastric pH: a crossover comparison with omeprazole. Scand J Gastroenterol. 1999; 34(4):341-5. DOI: 10.1080/003655299750026335. View

13.

Bell N, BURGET D, Howden C, Wilkinson J, Hunt R . Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion. 1992; 51 Suppl 1:59-67. DOI: 10.1159/000200917. View

14.

Lee R, Vakily M, Mulford D, Wu J, Atkinson S . Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel Dual Delayed Release formulation of a proton pump inhibitor--evidence for dosing flexibility. Aliment Pharmacol Ther. 2009; 29(8):824-33. DOI: 10.1111/j.1365-2036.2009.03979.x. View

15.

Metz D, Vakily M, Dixit T, Mulford D . Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy. Aliment Pharmacol Ther. 2009; 29(9):928-37. DOI: 10.1111/j.1365-2036.2009.03984.x. View

16.

Morelli G, Chen H, Rossiter G, Rege B, Lu Y . An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers. Aliment Pharmacol Ther. 2011; 33(7):845-54. DOI: 10.1111/j.1365-2036.2011.04580.x. View