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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