Rabeprazole 5 52 1.0–2.0 3.1 20 mg qd
GERD, gastroesophageal reflux disease; NA, data not available.
liver disease but should be considered in patients with severe liver impairment. Although other proton pumps exist in the body, the H+/K+-ATPase appears to exist only in the parietal cell and is distinct structurally and functionally from other H+-transporting enzymes.
The intravenous formulations of esomeprazole and pantoprazole have characteristics similar to those of the oral drugs. When given to a fasting patient, they inactivate acid pumps that are actively secreting, but they have no effect on pumps in quiescent, nonsecreting vesicles. Because the half-life of a single injection of the intravenous formulation is short, acid secretion returns several hours later as pumps move from the tubulovesicles to the canalicular surface. Thus, to provide maximal inhibition during the first 24–48 hours of treatment, the intravenous formulations must be given as a continuous infusion or as repeated bolus injections. The optimal dosing of intravenous PPIs to achieve maximal blockade in fasting patients is not yet established.
From a pharmacokinetic perspective, PPIs are ideal drugs: they have a short serum half-life, they are concentrated and activated near their site of action, and they have a long duration of action.
In contrast to H2 antagonists, PPIs inhibit both fasting and meal-stimulated secretion because they block the final common pathway of acid secretion, the proton pump. In standard doses, PPIs inhibit 90–98% of 24-hour acid secretion (Figure 62–2). When administered at equivalent doses, the different agents show little difference in clinical efficacy. In a crossover study of patients receiving long-term therapy with five PPIs, the mean 24-hour intragastric pH varied from 3.3 (pantoprazole, 40 mg) to 4.0 (esomeprazole, 40 mg), and the mean number of hours the pH was higher than 4 varied from 10.1 (pantoprazole, 40 mg) to 14.0 (esomeprazole, 40 mg). Although dexlansoprazole has a delayed-release formulation that results in a longer Tmax and greater AUC than other PPIs, it appears comparable to other agents in the ability to suppress acid secretion. This is because acid suppression is more dependent upon irreversible inactivation of the proton pump than the pharmacokinetics of different agents.
1. Gastroesophageal reflux disease—PPIs are the most effective agents for the treatment of erosive reflux disease, esophageal complications of reflux disease (peptic stricture or Barrett’s esophagus), and extraesophageal manifestations of reflux disease. Once-daily dosing provides effective symptom relief and tissue healing in 85–90% of patients; up to 15% of patients require twice-daily dosing.
GERD symptoms recur in over 80% of patients within 6 months after discontinuation of a PPI. For patients with erosive esophagitis or esophageal complications, long-term daily maintenance therapy with a full-dose or half-dose PPI is usually needed. Many patients with nonerosive GERD may be treated successfully with intermittent courses of PPIs or H2 antagonists taken as needed (“on demand”) for recurrent symptoms.
Drugs Used in the Treatment of Gastrointestinal Diseases 1093