Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors
[Display omitted] Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient’s CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this rev...
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| Published in | Pharmacological research Vol. 152; p. 104606 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
01.02.2020
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| Subjects | |
| Online Access | Get full text |
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| Abstract | [Display omitted]
Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient’s CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture. |
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| AbstractList | Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H
,K
-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H
,K
-ATPase and CYP2C19 polymorphisms, although gastric H
,K
-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture. Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture.Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture. [Display omitted] Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient’s CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture. |
| ArticleNumber | 104606 |
| Author | Liu, Jie Wang, Yong-Qing Zhou, Chen Zhang, Hong-Wen Zhang, He-Jian Zhang, Xue-Hui Liu, Yun Sun, Lu-Ning Xie, Li-Jun Shen, Yi-Wen Chen, Juan |
| Author_xml | – sequence: 1 givenname: He-Jian surname: Zhang fullname: Zhang, He-Jian organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 2 givenname: Xue-Hui surname: Zhang fullname: Zhang, Xue-Hui organization: Department of Pharmacy, Jiangsu Shengze Hospital, Nanjing Medical University, Suzhou, China – sequence: 3 givenname: Jie surname: Liu fullname: Liu, Jie organization: Pukou Branch, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China – sequence: 4 givenname: Lu-Ning surname: Sun fullname: Sun, Lu-Ning organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 5 givenname: Yi-Wen surname: Shen fullname: Shen, Yi-Wen organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 6 givenname: Chen surname: Zhou fullname: Zhou, Chen organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 7 givenname: Hong-Wen surname: Zhang fullname: Zhang, Hong-Wen organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 8 givenname: Li-Jun surname: Xie fullname: Xie, Li-Jun organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 9 givenname: Juan surname: Chen fullname: Chen, Juan organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 10 givenname: Yun surname: Liu fullname: Liu, Yun email: liuyun@njmu.edu.cn organization: Department of Geriatrics Endocrinology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China – sequence: 11 givenname: Yong-Qing surname: Wang fullname: Wang, Yong-Qing email: wyqjsph@163.com organization: Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University & Jiangsu Province Hospital, Nanjing, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31846760$$D View this record in MEDLINE/PubMed |
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| Keywords | homEMs Dexlansoprazole (PubChem CID: 9578005) Esomeprazole (PubChem CID: 9568614) H. pylori CYP2C19 AUC CYP450 t1/2 PMs SNPs Lansoprazole (PubChem CID: 3883) UMs Omeprazole (PubChem CID: 4594) Rabeprazole (PubChem CID: 5029) Gastric H+K+-ATPase Cmax Pharmacodynamics MR hetEMs PPIs Proton pump inhibitors (PPIs) Ilaprazole (PubChem CID: 214351) H+,K+-ATPase PD H2RAs Pantoprazole (PubChem CID: 4679) PK Pharmacokinetics TpH>4 (%) Polymorphism Gastric H(+)K(+)-ATPase |
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Pharmacol. doi: 10.1177/0091270011408611 – volume: 16 start-page: 1149 year: 2002 ident: 10.1016/j.phrs.2019.104606_bib0565 article-title: Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis publication-title: Aliment. Pharmacol. Ther. doi: 10.1046/j.1365-2036.2002.01270.x |
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Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance,... Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics... |
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| SubjectTerms | 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacology CYP2C19 Gastric H+K+-ATPase Humans Pharmacodynamics Pharmacogenomic Variants Pharmacokinetics Polymorphism Proton pump inhibitors (PPIs) Proton Pump Inhibitors - pharmacokinetics Proton Pump Inhibitors - pharmacology |
| Title | Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors |
| URI | https://dx.doi.org/10.1016/j.phrs.2019.104606 https://www.ncbi.nlm.nih.gov/pubmed/31846760 https://www.proquest.com/docview/2328350877 |
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