Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors

Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H+, K+-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, foll...

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Main Authors:	Shin, Jai Moo, Kim, Nayoung
Format:	Online
Language:	English
Published:	Korean Society of Neurogastroenterology and Motility 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548122/

id	pubmed-3548122
recordtype	oai_dc
spelling	pubmed-35481222013-01-24 Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors Shin, Jai Moo Kim, Nayoung Review Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H+, K+-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. 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. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. 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. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life. Korean Society of Neurogastroenterology and Motility 2013-01 2013-01-08 /pmc/articles/PMC3548122/ /pubmed/23350044 http://dx.doi.org/10.5056/jnm.2013.19.1.25 Text en © 2013 The Korean Society of Neurogastroenterology and Motility http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Shin, Jai Moo Kim, Nayoung
spellingShingle	Shin, Jai Moo Kim, Nayoung Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors
author_facet	Shin, Jai Moo Kim, Nayoung
author_sort	Shin, Jai Moo
title	Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors
title_short	Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors
title_full	Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors
title_fullStr	Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors
title_full_unstemmed	Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors
title_sort	pharmacokinetics and pharmacodynamics of the proton pump inhibitors
description	Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H+, K+-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. 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. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. 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. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.
publisher	Korean Society of Neurogastroenterology and Motility
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548122/
_version_	1611947932579266560

Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors

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