Rohss et al 2002 Wilder-Smith et al 2003 Wilder-Smith et al 2003 Miner et al 2003 Rohss et al 2004 Rohss et al 2004 Rohss et al 2004 Rohss et al 2004 Miehlke et al 2005 Johnson et al 2005 Double-blind, randomized, cross-over Open-label, randomized, cross-ove Open-label, randomized, cross-over Open-label, randomized, cross-over Open-label, randomized, cross-over Open-label, randomized cross-over Open-label, randomized, cross-over Open-label, randomized, cross-over Open-label, randomized, cross-over Single-blind, randomized, cross-over Open-label, randomized, cross-over Table 1 Gastric acidity, expressed as the percentage of time with intragastric pH >4.0 on day 5 in individuals treated with esomeprazole, omeprazole, pantoprazole, and rabeprazole in cross-over randomized pharmacodynamic studies Reference Study design Patient/individual PPIs compared Number of Percentage of time with selection individuals intragastric pH >4.0 Lind et al 2000 GERD symptoms Eso40 vs eso20 38 69.8% vs 53.0 vs vs ome 20 od 43.7% p < 0.01 GERD symptoms Eso40 vs ome 40 od 130 68.4% vs 62.0%, p < 0.001 Esomeprazole in GERD 65% vs 53%, p < 0.001 61% vs 45.1%, p = 0.005 58.4% vs 47% vs 49.1 vs 50.5%, p < 0.001 57.5% vs 44.6%, p < 0.0001 70% vs 43.8%, p < 0.0001 67.1% vs 45%, p < 0.001 59.6% vs 44.6%, p < 0.0001 85.4% vs 63.6%, p = 0.0001 81.3% vs 65.4% vs 60.1% vs 51.3% p < 0.05 Healthy volunteers Eso40 vs lan30 od Healthy volunteers Eso40 vs rabe20 od GERD symptoms GERD symptoms Eso40 vs lan30 vs ome20 vs panto40 vs rabe20 od Eso40 vs lan30 od GERD symptoms Eso40 vs ome20 od GERD symptoms Eso40 vs panto40 od GERD symptoms Eso40 vs rabe20 od Healthy volunteers Eso40 vs panto bd GERD symptoms Eso40 bd vs lan30 bd vs eso40 od vs lan30 od 24 23 34 36 38 32 35 30 45 Abbreviations: Eso, esomeprazole; GERD, gastroesophageal reﬂux disease; lan, lansoprazole; ome, omeprazole; PPI, proton-pump inhibitor; panto, pantoprazole; rabe, rabeprazole. esophageal dysmotility, and Barrett’s esophagus (DeVault and Castell 2005). A recent double-blind, randomized, cross- over study investigated the 24-hour intragastric pH proﬁle of esomeprazole 40 mg bd vs 20 mg bd vs 40 mg od in 25 healthy volunteers (Katz et al 2004). Esomeprazole 40 mg bd provided a mean time of 19.2 hours with intragastric pH 4.0 (80.1% of a 24-hour time period, 95% conﬁdence interval (CI) 74.5%–85.7%) vs 14.2 hours with 40 mg od (59.2%, 95% CI 53.7%–64.7%) and 17.5 hours with 20 mg bd (73.0%, 95% CI 67.4%–78.5%). The percentage of time of a 24-hour period that pH remained 4.0 was significantly higher with the esomeprazole bd dosing regimens compared to the 40 mh od regimen during the supine (sleeping) portion of the monitoring period (83.7% (95% CI 74.9%–92.4%) for esomeprazole 40 mg bd vs Therapeutics and Clinical Risk Management 2007:3(4) 79.2% (95% CI 70.5%–87.9%) for esomeprazole 20 mg bd vs 57.9% (95% CI 49.0%–66.9%) for esomeprazole 40 mg od (Katz et al 2004). Esomeprazole 40 mg bd has also been shown to be superior to pantoprazole 40 mg bd and lansoprazole 30 mg bd in maintaining intragastric pH at 4.0 or lower (Table 1). These data indicate that twice-daily dosing of omeprazole provides signiﬁcantly greater acid suppression than once-daily dosing and may, therefore, be a reasonable consideration for patients requiring greater acid-suppression for GERD. The effects of esomeprazole on esophageal acidity Two studies have assessed the effect of esomeprazole on intraesophageal pH proﬁles compared to other PPIs. 655