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Relation of cytochrome P450 2C19 gene 681G>A single nucleotide polynmrphism to clopidogrel resistance after PCI in Chinese
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作者 LIANG Zhen-yang,HAN Ya-ling,ZHANG Xiao-lin,YAN Cheng-hui (Department of Cardiology,Cardiovascular Institute of PLA, Shenyang Northern Hospital.Shenyang 110031,China) 《岭南心血管病杂志》 2011年第S1期155-155,共1页
Objectives Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450(CYP) isoenzymes to inhibit platelet aggregation.Individualvariability of platelet inhibition by clopidogr... Objectives Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450(CYP) isoenzymes to inhibit platelet aggregation.Individualvariability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness.In this study,we sought to determine the association between the single nucleotide polymorphism of CYP 2C19 681G】A and the occurrence of clopidogrel resistance(CR) in Chinese.Methods The study enrolled 614 hospitalized patients who underwentsuccessful percutaneouscoronary intervention with drug-eluting stents were received the treatmentwith dual antiplatelet regimen(aspirin plus clopidogrel).All patients received loading doses of 600 mg clopidogrel and 300 mg aspirin.20μmol/L ADP-induced platelet aggregation ratio(PAR ) was assessed 24 h after clopi- dogrel administration.The maximum residual PAR≥70%was defined as CR.Genomic DNA was extracted from whole blood samples according to standard protocols,the single nucleotide polymorphism of the CYP2C19 681G】A was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all the patients.Results CR was found in 126 patients(20.5%).There was CYP2C19 681G】A polymorphism in the study population.The frequencies of the three kinds of genotypes(GG,GA,A A) in CR group and non-CR (NCR)group were 32.5%,47.6%,19.8%and 48.0%, 45.0%,7.0%,respectively.The frequency of AA genotype was significantly higher in NCR group than that in CR group (OR =3.03,95%CI:1.889~5.784,P=0.003).The A allele carriers were more likely to develop clopidogrel resistance compared with that of G allele carriers(OR=1.85,95%CI: 1.392~2.459,P=0.002).Conclusions CYP2C19 681G/A polymorphism is associated with the risk of CR,and the A allele carriers may be a possible genetic susceptibility factor for patients with CR. 展开更多
关键词 PCI Relation of cytochrome P450 2c19 gene 681G>A single nucleotide polynmrphism to clopidogrel resistance after PCI in Chinese GENE
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Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype 被引量:29
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作者 Mitsushige Sugimoto Takahisa Furuta 《World Journal of Gastroenterology》 SCIE CAS 2014年第21期6400-6411,共12页
The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacter... The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH &#x0003e; 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1&#x003b2;). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates. 展开更多
关键词 Helicobacter pylori Tailored eradication therapy Proton pomp inhibitor cytochrome P450 2c19 CLARITHROMYCIN
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Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers 被引量:2
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作者 Hatsushi Yamagishi Tomoyuki Koike +10 位作者 Shuichi Ohara Toru Horii Ryousuke Kikuchi Shigeyuki Kobayashi Yasuhiko Abe Katsunori Iijima Akira Imatani Kaori Suzuki Takanori Hishinuma Junichi Goto Tooru Shimosegawa 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第13期2049-2054,共6页
AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-neg... AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was perform- ed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg. 展开更多
关键词 LPZ 30 mg orally disintegrating tablets Intragastric pH Blood drug concentration cytochrome P450 2c19 extensive metabolizers H pylori-negative
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Maintenance time of sedative effects after an intravenous infusion of diazepam: A guide for endoscopy using diazepam
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作者 Mitsushige Sugimoto Takahisa Furuta +8 位作者 Akiko Nakamura Naohito Shirai Mutsuhiro Ikuma Shingen Misaka Shinya Uchida Hiroshi Watanabe Kyoichi Ohashi Takashi Ishizaki Akira Hishida 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第33期5197-5203,共7页
AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP ) 2C19 genotypes after an infusion regimen of diazepam commonly used forgastrointestinal endoscopy in... AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP ) 2C19 genotypes after an infusion regimen of diazepam commonly used forgastrointestinal endoscopy in Japan. METHODS: Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical ? icker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg). RESULTS: The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P < 0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests. CONCLUSION: With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within 1 h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved. 展开更多
关键词 DIAZEPAM SEDATION cytochrome P450(CYP) 2c19 ENDOSCOPY Complication Critical flicker fusion test Eye movement analysis Postural sway test Visual analog scale
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Effect and safety of anaprazole in the treatment of duodenal ulcers:a randomized,rabeprazole-controlled,phase Ⅲ non-inferiority study 被引量:2
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作者 Huiyun Zhu Xue Pan +10 位作者 Li Zhang Hongxin Sun Huizhen Fan Zhongwei Pan Caibin Huang Zhenwang Shi Jin Ding Qi Wang Yiqi Du Nonghua Lyu Zhaoshen Li 《Chinese Medical Journal》 SCIE CAS CSCD 2022年第24期2941-2949,共9页
Background:The pharmacokinetic and clinical behaviors of many proton pump inhibitors(PPIs)in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms.This non-inferiority study evaluated the efficacy and sa... Background:The pharmacokinetic and clinical behaviors of many proton pump inhibitors(PPIs)in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms.This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole.We also explored the influence of Helicobacter pylori(H.pylori)infection status and CYP2C19 polymorphism on anaprazole.Methods:In this multicenter,randomized,double-blind,double-dummy,positive-drug parallel-controlled,phase Ⅲ study,Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg+anaprazole placebo or rabeprazole placebo+anaprazole 20 mg once daily for 4 weeks.The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review.Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks.Furthermore,exploratory subgroup analysis of the primary endpoint by H.pylori status and CYP2C19 polymorphism was conducted.Adverse events were monitored for safety.Non-inferiority analysis was conducted for the primary endpoint.Results:The study enrolled 448 patients(anaprazole,n=225;rabeprazole,n=223).The 4-week healing rates were 90.9%and 93.7%for anaprazole and rabeprazole,respectively(difference,-2.8%[95%confidence interval,-7.7%,2.2%]),demonstrating non-inferiority of anaprazole to rabeprazole.Overall duodenal ulcer symptoms improved in 90.9%and 92.5%of patients,respectively.Improvement rates of individual symptoms were similar between the groups.Healing rates did not significantly differ by H.pylori status or CYP2C19 genotype for either treatment group.The incidence of treatment-emergent adverse events was similar for anaprazole(72/220,32.7%)and rabeprazole(84/219,38.4%).Conclusions:The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration:ClinicalTrials.gov,NCT04215653. 展开更多
关键词 cytochrome P-450 CYP2c19 Non-inferiority trial Peptic ulcer POLYMORPHISM Genetic Proton pump inhibitors Anaprazole RABEPRAZOLE
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