Longest Acting Proton Pump Inhibitor
Potassium-competitive acid blockers (P-CABs), such as vonoprazan and tegoprazan, are the longest acting acid suppressants available, with half-lives of 6-9 hours compared to 1-2 hours for traditional PPIs, allowing them to maintain target intragastric pH levels for longer proportions of a 24-hour period. 1
P-CABs vs Traditional PPIs: Duration of Action
Among traditional PPIs, dexlansoprazole modified release (MR) provides the longest duration of acid suppression due to its dual delayed release formulation that produces two peak plasma concentrations (at 2 and 5 hours post-dose), maintaining therapeutic drug levels longer than any other conventional PPI. 2, 3
Key Pharmacokinetic Differences:
P-CABs (vonoprazan, tegoprazan): Half-life of 6-9 hours, providing prolonged gastric acid inhibition and maintaining target pH levels for extended periods throughout the 24-hour cycle 1
Dexlansoprazole MR: Longest acting traditional PPI with dual-peak pharmacokinetics that extends plasma concentration-time profile beyond single-release formulations 2, 3
Standard PPIs: Half-life of 1-2 hours (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) 1
Clinical Implications
P-CABs achieve maximal acid suppression with once-daily dosing within 1 day, whereas traditional PPIs require 3-5 days to reach steady-state effectiveness. 1 This is because P-CABs are not prodrugs and do not require acid activation or conversion to an active form, plus they are not metabolized by CYP2C19, eliminating genetic variability in drug response. 1
Relative Potency Among Traditional PPIs:
When comparing standard PPIs by omeprazole equivalency: 1, 4
- Rabeprazole 20 mg = 36 mg omeprazole
- Esomeprazole 20 mg = 32 mg omeprazole
- Lansoprazole 30 mg = 27 mg omeprazole
- Pantoprazole 40 mg = 9 mg omeprazole (least potent)
Important Caveats
While P-CABs provide longer duration of action, they are not first-line therapy for most acid-related conditions. 1 Current AGA guidelines recommend P-CABs primarily for PPI-refractory GERD (LA grade C/D erosive esophagitis failures), peptic ulcer disease, and H. pylori eradication therapy. 1
Traditional PPIs require dosing 30-60 minutes before meals for optimal efficacy, whereas P-CABs can be taken independent of mealtimes due to their longer half-lives and acid stability. 1, 5
Serum gastrin levels rise higher with P-CABs compared to PPIs and remain elevated throughout treatment duration, though long-term safety data through 5 years show comparable adverse event profiles. 1