Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors.
- Author:
Jai Moo SHIN
1
;
Nayoung KIM
Author Information
1. Jai Scientific, Los Angeles, California, USA. jaimooshin@gmail.com
- Publication Type:Review
- Keywords:
Area under the plasmic concentration curve;
Hydrogen potassium ATPase;
Gastric acid;
Gastric endogenous activator protein, mammal;
Pharmacokinetics;
Pharmacology;
Proton pump inhibitors
- MeSH:
2-Pyridinylmethylsulfinylbenzimidazoles;
Benzimidazoles;
Gastric Acid;
Genotype;
Half-Life;
Hydrogen-Ion Concentration;
Imidazoles;
Nitro Compounds;
Omeprazole;
Proton Pump Inhibitors;
Proton Pumps;
Protons;
Pyridines;
Quality of Life
- From:Journal of Neurogastroenterology and Motility
2013;19(1):25-35
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
