Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects
Background: Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00670/full |
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| author | Lu-Ning Sun Yang Cao Yue-Qi Li Yun-Qian Fang Hong-Wen Zhang Mei-Feng Wang Li-Jun Xie Juan Chen Zhi-Cheng Yang Ming-Liang Bian Hao Li Pei-Pei Zhang Ji-Fu Wei Ling Meng Xue-Hui Zhang Ping Zhao Yong-Qing Wang Yong-Qing Wang |
| author_facet | Lu-Ning Sun Yang Cao Yue-Qi Li Yun-Qian Fang Hong-Wen Zhang Mei-Feng Wang Li-Jun Xie Juan Chen Zhi-Cheng Yang Ming-Liang Bian Hao Li Pei-Pei Zhang Ji-Fu Wei Ling Meng Xue-Hui Zhang Ping Zhao Yong-Qing Wang Yong-Qing Wang |
| author_sort | Lu-Ning Sun |
| collection | DOAJ |
| description | Background: Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric H+/K+-ATPase, CYP2C19, and ABCB1 polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects.Methods: A total of 51 subjects were enrolled for pharmacokinetic and pharmacodynamic study after a single intravenous administration of 20 or 30 mg dexlansoprazole. Plasma concentrations were determined using a chiral liquid chromatography-mass spectrometry method. The intragastric pH and baseline-adjusted intragastric pH parameters were introduced to evaluate the pharmacodynamic characters. Genotyping was performed by polymerase chain reaction.Results: The pharmacokinetic parameters were significantly influenced by CYP2C19 phenotypes, and gastric acid secretion inhibition were affected by both gastric H+/K+-ATPase and CYP2C19 polymorphisms. Gastric H+/K+-ATPase genotypes had greater effects than CYP2C19 genotypes on the suppression of gastric acid secretion.Conclusion: Gastric H+/K+-ATPase polymorphism may be one of the main reasons that cause insufficient gastric acid inhibition. |
| first_indexed | 2024-12-22T04:46:59Z |
| format | Article |
| id | doaj.art-8982e77b08fb442cab61ad012d66e36d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T04:46:59Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-8982e77b08fb442cab61ad012d66e36d2022-12-21T18:38:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-09-01810.3389/fphar.2017.00670291416Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese SubjectsLu-Ning Sun0Yang Cao1Yue-Qi Li2Yun-Qian Fang3Hong-Wen Zhang4Mei-Feng Wang5Li-Jun Xie6Juan Chen7Zhi-Cheng Yang8Ming-Liang Bian9Hao Li10Pei-Pei Zhang11Ji-Fu Wei12Ling Meng13Xue-Hui Zhang14Ping Zhao15Yong-Qing Wang16Yong-Qing Wang17Research Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaDepartment of Gastroenterology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaDepartment of Gastroenterology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaDepartment of Pharmacy, Jiangsu Shengze HospitalSuzhou, ChinaDepartment of Pharmacy, Jiangsu Shengze HospitalSuzhou, ChinaResearch Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical UniversityNanjing, ChinaDepartment of Pharmacy, Jiangsu Shengze HospitalSuzhou, ChinaBackground: Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric H+/K+-ATPase, CYP2C19, and ABCB1 polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects.Methods: A total of 51 subjects were enrolled for pharmacokinetic and pharmacodynamic study after a single intravenous administration of 20 or 30 mg dexlansoprazole. Plasma concentrations were determined using a chiral liquid chromatography-mass spectrometry method. The intragastric pH and baseline-adjusted intragastric pH parameters were introduced to evaluate the pharmacodynamic characters. Genotyping was performed by polymerase chain reaction.Results: The pharmacokinetic parameters were significantly influenced by CYP2C19 phenotypes, and gastric acid secretion inhibition were affected by both gastric H+/K+-ATPase and CYP2C19 polymorphisms. Gastric H+/K+-ATPase genotypes had greater effects than CYP2C19 genotypes on the suppression of gastric acid secretion.Conclusion: Gastric H+/K+-ATPase polymorphism may be one of the main reasons that cause insufficient gastric acid inhibition.http://journal.frontiersin.org/article/10.3389/fphar.2017.00670/fullgastric H+/K+-ATPasegastric acidpharmacokineticspharmacogenomicsCYP2C19 |
| spellingShingle | Lu-Ning Sun Yang Cao Yue-Qi Li Yun-Qian Fang Hong-Wen Zhang Mei-Feng Wang Li-Jun Xie Juan Chen Zhi-Cheng Yang Ming-Liang Bian Hao Li Pei-Pei Zhang Ji-Fu Wei Ling Meng Xue-Hui Zhang Ping Zhao Yong-Qing Wang Yong-Qing Wang Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects Frontiers in Pharmacology gastric H+/K+-ATPase gastric acid pharmacokinetics pharmacogenomics CYP2C19 |
| title | Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects |
| title_full | Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects |
| title_fullStr | Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects |
| title_full_unstemmed | Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects |
| title_short | Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects |
| title_sort | impact of gastric h k atpase rs2733743 on the intragastric ph values of dexlansoprazole injection in chinese subjects |
| topic | gastric H+/K+-ATPase gastric acid pharmacokinetics pharmacogenomics CYP2C19 |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00670/full |
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