Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies.
Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies.
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DOI：
10.2133/dmpk.20.153
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发表时间：
2005-06-01
影响因子：
2.1
通讯作者：
Ishizaki, Takashi
中科院分区：
文献类型：
--
作者：
Furuta, Takahisa;Shirai, Naohito;Ishizaki, Takashi
质子泵抑制剂（PPI），如奥美拉唑、兰索拉唑、雷贝拉唑、埃索美拉唑和泮托拉唑，主要由肝脏中的CYP2C19代谢。这种酶的活性存在遗传决定的差异。 CYP2C19的基因型分为三组：快代谢型(RM)、中代谢型(IM)和慢代谢型(PM)。 PPI 的药代动力学和药效学取决于 CYP2C19 基因型状态。 RM组中PPI治疗期间的血浆PPI水平和胃内pH值最低，IM组次之，PM组最高。 PPI 的药代动力学和药效学中的这些 CYP2C19 基因型依赖性差异影响基于 PPI 的治疗对胃食管反流病和幽门螺杆菌感染的治愈率。为了获得更好的基于 PPI 的治疗，应根据 CYP2C19 基因型状态优化 PPI 的剂量和给药方案。
Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are mainly metabolized by CYP2C19 in the liver. There are genetically determined differences in the activity of this enzyme. The genotypes of CYP2C19 are classified into the three groups, rapid extensive metabolizer (RM), intermediate metabolizer (IM), and poor metabolizer (PM). The pharmacokinetics and pharmacodynamics of PPIs depend on CYP2C19 genotype status. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs influence the cure rates for the gastro-esophageal reflux disease and H. pylori infection by PPI-based therapies. For the better PPI-based treatment, doses and dosing schemes of PPIs should be optimized based on CYP2C19 genotype status.