The prediction of Helicobacter Pylori eradication using CYP2C19 activity determined by limited plasma concentration of omeprazole enantiomers

利用奥美拉唑对映体有限血浆浓度确定的 CYP2C19 活性预测幽门螺杆菌根除

• 批准号: 20590150
• 负责人: UNO Tsukasa
• 金额: $ 2.91万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590150/
• 关键词: 薬物動態; 代謝学; CYP2C19; AUC; HPLC; オメプラゾール; オメプラゾール光学異性体

Until now, no studies investigating the in vivo metabolic behaviour of omeprazole enantiomers have been reported. The three major metabolites of omeprazole, known as (R)-,(S)-5-hydroxyomeprazole and omeprazole sulfone, are mainly metabolised by cytochrome P450 (CYP) 2C19 and CYP3A4, respectively. The clinical efficacy of Helicobacter Pylori eraducation is closely related to the CYP2C19 phenotypes, as evidenced by studies in patients receiving omeprazole. In the present study, we constructed a simple and sensitive high-performance liquid chromatography (HPLC) UV method and it used in pharmacokinetic studies of (R)- and (S)-omeprazole and their chiral metabolites in relation to the CYP2C19 genotypes. Conceqently, CYP2C19 genotypes were clarified and the prediction of CYP2C19 genotypes by using limited plasma concentration of omeprazole enantiomers may be a important tool in clinical situation.

到目前为止，还没有关于奥美拉唑对映体体内代谢行为的研究报道。奥美拉唑的三种主要代谢产物(R)-、(S)-5-羟基奥美拉唑和奥美拉唑砜分别主要由细胞色素P450(CYP)2C19和细胞色素P3A4代谢。根除幽门螺杆菌的临床疗效与CYP2C19表型密切相关，接受奥美拉唑治疗的患者的研究证明了这一点。在本研究中，我们建立了一种简单、灵敏的高效液相色谱法，并将其用于(R)和(S)奥美拉唑及其手性代谢物的药代动力学研究。因此，用奥美拉唑对映体的血药浓度限值来预测CYP2C19的基因分型可能是临床上的一项重要工具。

项目成果

PGP-MEDIATED EFFECTS OF ITRACONAZOLE AND CARBAMAZEPINE ON FEXOFENADINE ENANTIOMERS PHARMACOKINETICS

PGP 介导的伊曲康唑和卡马西平对非索非那定对映体药代动力学的影响

• 发表时间: 2009
• 作者: Niioka T;Miura M;Uno I;Yasui-Furukori N;Hayakari M;Tateishi T;Suzuki T;潮平英郎;潮平英郎;赤嶺由美子
• 通讯作者: 赤嶺由美子

Comparison of drug sensitivity and genotypes of clinically isolated strains of levofloxacin-resistant Streptococcus pneumoniae obtained from Okinawa Island, the Japanese main island and Hong Kong

• DOI: 10.1038/ja.2011.46
• 发表时间: 2011-08
• 期刊: The Journal of Antibiotics
• 作者: S. Sunagawa;J. Fujita;F. Higa;M. Tateyama;Shusaku Haranaga;I. Nakasone;N. Yamane;Tsukasa Uno

The effect of CYP2C19 genotypes on the pharmacokinetics of warfarin enantiomers

CYP2C19基因型对华法林对映体药代动力学的影响

• 发表时间: 2008
• 期刊: Journal of Clinical Pharmacy and Therapeutics
• 影响因子: 2
• 作者: T. Uno;K. Sugimoto;K. Sugawara;T. Tateishi
• 通讯作者: T. Tateishi

ラベプラゾールとその主代謝物の高感度定量によるCYP2C19遺伝子型に関連したCYP3AまたはP-gp阻害剤とのin vivo併用効果

雷贝拉唑及其主要代谢物与CYP3A或P-gp抑制剂的体内联合作用与CYP2C19基因型的关系

• 发表时间: 2008
• 作者: Niioka T;Miura M;Uno I;Yasui-Furukori N;Hayakari M;Tateishi T;Suzuki T;潮平英郎;潮平英郎;赤嶺由美子;赤嶺由美子;外間惟夫
• 通讯作者: 外間惟夫

A sensitive column-switching HPLC method for aripiprazole and dehydroaripiprazole and its application to human pharmacokinetic studies

• DOI: 10.1002/jssc.201000457
• 发表时间: 2010-11-01
• 期刊: JOURNAL OF SEPARATION SCIENCE
• 影响因子: 3.1
• 作者: Akamine, Yumiko;Yasui-Furukori, Norio;Uno, Tsukasa
• 通讯作者: Uno, Tsukasa