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PPIs versus P-CABs

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PPIs versus P-CABs

P-CABs like linaprazan works differently from traditional PPI-based drugs like Losec and Nexium. Let us clarify how they manage to block the acid to maintain a normal pH.

 

The Proton Pump Inhibitor (PPI)

The PPI is absorbed in the small intestine and reach the parietal cell via blood. Since the PPI’s are weak bases, they will accumulate in the acid compartment of the parietal cell and they will there be converted to the active inhibitor (sulfenamide). They will rapidly bind to the H+, K+-ATPase with a covalent binding and form an irreversible inhibition. Due to the short plasma half-life of the PPI’s, they will not be able to control intragastric pH during the 24 hour period. The PPI’s are characterized by their slow onset of action and require 3-5 days to reach full effect.



  • Plasma half-life is 1-1.5 hours

  • Up to three times daily – duration still less than 18 hours

  • Slow onset to maximum effect (3-5 days)

  • Prodrugs that require acid for activation yet are unstable in acidic conditions


Potassium-Competitive Acid Blocker (P-CAB) – linaprazan glurate

Linaprazan glurate and other P-CAB’s are absorbed in the small intestine and reach the parietal cell via blod. Also the P-CAB’s are weak bases and will also accumulate in the parietal cell. After protonation it will bind to the H+, K+-ATPase with an ionic binding and form a competitive inhibition. This will offer more flexibility compared to the irreversible inhibition and a possibility to tailor the duration of acid control.

Linaprazan glurate has a plasma half-life of approximately 10 hours and have been shown to provide 24 hour control of intragastric pH. The P-CAB’s are characterized by a rapid onset of action and neutral intragastric pH has been demonstrated two hours after the first dose with linaprazan glurate to healthy volunteers.

cinclus linaprazan P-CAB in plasma

  • Plasma half-life is 5-10 hours

  • Once or twice daily provides 24h acid control

  • Fast onset (~1-2 hour)

  • No activation required and stable in acidic conditions

 

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