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Relative Potency of Proton-Pump Inhibitors

Information sourced from NEJM Journal Watch:

Relative Potency of Proton-Pump Inhibitors

Very high PPI doses and three times daily administration do not increase the duration of gastric acid suppression.

Various proton-pump inhibitors (PPIs) are used in different doses to achieve similar clinical results. To suggest ideal dosing regimens of different PPIs, investigators performed a meta-analysis of 56 randomized trials that compared PPI doses to changes in gastric pH.

The analysis included a total of 3713 patients in 146 study groups who took PPIs once daily (116 groups), twice daily (25 groups), or three times daily (5 groups). Median daily time with a [gastric pH >4 (pH4 time)] was compared among the groups after 5 days of oral PPI administration. Data were reviewed based on previously determined omeprazole equivalents (OEs; Eur J Clin Pharmacol 2009; 65:19), ranging from 4.5 mg of pantoprazole to 36 mg of rabeprazole being equivalent to 20 mg of omeprazole.

Increasing once daily doses of PPIs from 9 mg OE to 60 mg OE increased the pH4 time linearly from 10 hours to 18.5 hours, with no advantage for doses higher than 60 mg OE. Twice or three times daily PPI dosing increased median pH4 time linearly from 15.8 to 21 hours. There was no advantage of three times a day dosing versus twice daily. The authors noted that generic forms of PPIs were the most cost-effective. They conclude that the use of OEs and these data allow clinicians to tailor PPI choice and dosing to provide the lowest effective dose.


Gastric acid secretion has long been used as a surrogate marker for efficacy of PPIs. We must remember that changes in gastric pH do not always correlate with clinical results. These results show that very high OEs (over 60 mg) do not provide better acid suppression and that three times daily dosing has no benefit over twice daily dosing.

David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) reviewing Graham DY and Tansel A. Clin Gastroenterol Hepatol 2017 Sep 27.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


Graham DY and Tansel A. [Interchangeable] use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 2017 Sep 27; [e-pub]. [PubMed® abstract]

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