Potassium-competitive acid blockers and gastroesophageal reflux disease

Table 1 Main differences in the mechanisms of action between proton pump inhibitors and potassium-competitive acid blockers[12]

Proton pump inhibitors	Potassium-competitive acid blockers
Prodrug requires transformation to the active form, sulphenamide	Direct action on the H+/K+ ATPase after protonation
Sulphenamide binds covalently to H+/K+-ATPase	P-CABs bind competitively to the K+ binding site of H+/K+-ATPase
Irreversible binding to the proton pump	Reversible binding to the proton pump
The full effect after repeated doses	The full effect after the first dose
PK affected by genetic polymorphism	PK not affected by genetic polymorphism
PD effect more significant during the daytime	PD effect lasting for both the daytime and nocturnal hours
Meal-dependent antisecretory activity	Meal-independent antisecretory activity
Concentrate in parietal cell acid space (1000-fold higher than in plasma)	Super concentrates in parietal cell acid space (100000-fold higher than in plasma)
Duration of effect related to the half-life of the sulphenamide-enzyme complex	Duration of effect related to the half-life of the drug in plasma

P-CAB: Potassium-competitive acid blocker; PD: Pharmacodynamic; PK: Pharmacokinetic.