Relative Efficacies of Gastric Proton-Pump Inhibitors on a Milligram Basis: Desired and Undesired SH reactions. Impact of Chirality

Gastric proton-pump inhibitors (PPIs) are prodrugs. Their acid activation at pH 1.0 inside the canaliculus of a parietal cell should be fast relative to their serum elimination rate. Actually, all PPIs display chemical activation half-lives at pH 1.0 of a few minutes at the most, while being eliminated from serum with a half-life of about 1 h. This is the main reason they show similar antisecretory efficacies on a milligram basis. It is in line with about 5% to 15% higher healing rates in GERD, DU and GU when 40 mg is compared to 20 mg of either omeprazole or pantoprazole. The comparably large biological variation between patient samples explains why some studies show statistically significant differences between the two doses, while others do not. However, it would matter to the individual patient if s/he was the one additionally healed by a 40 mg dose within a defined treatment period. Chemical activation of PPI prodrugs is unwanted in weakly acidic tissue compartments such as lysosomes or secretory gra...