Interchangeable Use of Proton Pump Inhibitors Based on Relative Potency

Abstract

Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials that performed pH testing in patients receiving solid-dose PPI formulations (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) for a minimum of 5 days. We used omeprazole equivalency and the surrogate biomarker, percentage time pH > 4 over a 24-hour period (pH4time), to compare PPI effectiveness for different PPIs given once, twice, or 3 times daily. We found that increasing strength of once-daily PPIs (9-64 mg omeprazole equivalents) increased pH4time linearly from approximately 10.0 to 15.6 hours; higher doses produced no further increase in pH4time. Increasing the frequency to twice-daily PPI increased pH4time linearly, from approximately 15.8 to 21.0 hours. Three-times daily PPIs performed similarly to twice-daily PPIs. The costs of PPIs varied greatly, but the cost variation was not directly related to potency. We conclude that PPIs can be used interchangeably based on potency. Using twice-daily PPIs is more effective in increasing efficacy increasing once-daily PPI dosage. Omeprazole and lansoprazole (30 mg) and 20 mg of esomeprazole rabeprazole are functionally equivalent.

Keywords: Drug; Efficacy Comparison; GERD; Reflux; Treatment.

Figure 1.

The effect of different PPIs given once daily as OEs on the proportion of the day the intragastric pH remained at 4 or higher. Data are presented as weighted medians and 95% CIs as omeprazole equivalents ranging from 2.5 mg OE/d to 128 mg OE/d. All data are after at least 5 days of therapy in Western populations.

Figure 2.

(A) Comparison of the effects of once-daily and twice-daily PPI administration as OEs on the proportion of the day the intragastric pH remained at 4 or higher. Once-a-day PPI ranged from 9 to 64 mg OEs. Twice-daily administration ranged from 18 to 64 mg OEs. For both, the linear regression line is shown and for twice-daily administration the 95% CI is shown. All data are after at least 5 days of therapy in Western populations. (B) Comparison of the effects of once-daily, twice-daily (solid black symbols), and 3 times/d (open symbols) administration as OEs on the proportion of the day the intragastric pH remained at 4 or higher. The regression line for twice-daily and 3 times/d administration superimpose each other. bid, twice daily; tid, 3 times/d.

Figure 3.

Comparison of the effectiveness of various PPIs in maintaining the median pH at 6 or higher for 24 hours (pH6time) when given once, twice, or 3 times daily (Supplementary Table 4 for details). bid, twice daily; tid, 3 times/d.

Figure 4.

Effect of dexlansoprazole, a quasi–twice-daily therapy, on maintaining the intragastric pH level at 4 or higher.