In the canaliculus, the gastric H +, K +-ATPase can access KCl of the extracellular region and exchange the intracellular proton with the extracellular K ion, which represents the gastric acid secretion. One effect of PKA activation is the phosphorylation of cytoskeletal proteins involved in the transport of the gastric H +, K +-ATPase from cytoplasm to the plasma membrane, i.e., from the vesicular and/or tubular vesicular membrane to the canaliculus. 1, 2 Histamine binds to the H2 receptor, leading to elevation of intracellular cyclic AMP concentrations and activation of protein kinase A (PKA). The major functional targets in the parietal cell were the histamine type 2 (H2) receptor and the gastric H +, K +-ATPase. Since the parietal cell was known to secrete gastric acid, many drugs were developed to target the parietal cell in order to inhibit the acid secretion. Keywords: Area under the plasmic concentration curve, Hydrogen potassium ATPase, Gastric acid, Gastric endogenous activator protein, mammal, Pharmacokinetics, Pharmacology, Proton pump inhibitors Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Similarly, R-lansoprazole was developed in order to increase the drug activity. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. PPIs have about 1hour of elimination half-life. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. ![]() Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Activated PPI binds covalently to the gastric H +, K +-ATPase via disulfide bond. Proton pump inhibitor (PPI) is a prodrug which is activated by acid.
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