Duration of Action of Vonaprazan
Vonaprazan maintains acid suppression for over 24 hours after a single 20 mg dose, with an elimination half-life of approximately 6.8-7.7 hours. 1, 2
Pharmacodynamic Duration
The antisecretory effect of vonaprazan begins within 2-3 hours after a single 20 mg dose and is maintained for over 24 hours. 1
Following discontinuation of therapy, the intragastric pH remains elevated compared to placebo for 24 to 48 hours after the final dose on Day 7, demonstrating prolonged pharmacodynamic effects that outlast plasma drug levels. 1
At steady state (achieved by Day 3-4), vonaprazan maintains the 24-hour intragastric pH >4 holding time ratio at 83% on Day 7 of repeated 20 mg once-daily dosing. 2
Pharmacokinetic Half-Life
The mean apparent terminal elimination half-life is 6.8-7.7 hours in healthy adults at steady state. 1, 2
Despite this relatively short plasma half-life, vonaprazan accumulates and is retained in the stomach for more than 24 hours, even after elimination from plasma, explaining the prolonged duration of action. 3
Mechanism Explaining Prolonged Action
Vonaprazan is a potassium-competitive acid blocker (P-CAB) with reversible but slow dissociation from the H+,K+-ATPase receptor, which contributes to its extended duration of effect. 4, 1
Being a base with pKa of 9.6 and acid-resistant properties, vonaprazan concentrates highly in the acidic canaliculi of gastric parietal cells, allowing it to elicit acid suppression for longer than 24 hours after a 20 mg dose. 2
The drug inhibits TRAP-induced platelet aggregation for up to 4 weeks in the context of vorapaxar (a different PAR-1 antagonist), though this refers to a different drug class and should not be confused with vonaprazan's gastric acid suppression duration. 4