cytochrome p450 2c19
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2021 ◽  
Vol 12 ◽  
Author(s):  
Yuko Morino ◽  
Mitsushige Sugimoto ◽  
Naoyoshi Nagata ◽  
Ryota Niikiura ◽  
Eri Iwata ◽  
...  

Background: Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy.Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included.Results: A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8–80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3–79.6%), 81.2% (1,498/1,844, 95% CI: 79.3–83.0%) and 86.8% (644/742, 95% CI: 83.9–88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06–1.39, P = 0.006) and 1.57 (95% CI: 1.27–1.94, P < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (P < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar.Conclusion: The cure rates of PPI-amoxicillin-clarithromycin H. pylori eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.


2021 ◽  
Vol 5 (1) ◽  
pp. 19
Author(s):  
Adriana M. L. Ferraz ◽  
Susana Bandarra ◽  
Paulo Mascarenhas ◽  
Isabel Barahona ◽  
Rui Martins ◽  
...  

The interindividual variability of Proton Pump Inhibitor (PPI) therapy results from the phenotype variability associated with the cytochrome P450 2C19 (CYP2C19) gene, namely the CYP2C19*17 allele. Our aim was to characterize patients’ genetic variability undergoing PPI therapy. A sample of 33 oral mucosa cells from Portuguese pharmacy patients was collected, followed by genotyping. The allelic frequencies of CYP2C19*1 (-806C) and CYP2C19*17 (-806T) were 71.2% and 28.8%, respectively. The genotypic frequencies for CYP2C19*1/*1 and CYP2C19*1/*17 were 42.4% and 57.6%, respectively, and 19 of these patients may have a Rapid Metabolizer (RM) phenotype pharmaceutical opinion letter, based on genetic evidence.


2021 ◽  
Vol 10 (10) ◽  
pp. 2089
Author(s):  
Léa Bolcato ◽  
Charles Khouri ◽  
Anette Veringa ◽  
Jan Willem C. Alffenaar ◽  
Takahiro Yamada ◽  
...  

Few studies have simultaneously investigated the impact of inflammation and genetic polymorphisms of cytochromes P450 2C19 and 3A4 on voriconazole trough concentrations. We aimed to define the respective impact of inflammation and genetic polymorphisms on voriconazole exposure by performing individual data meta-analyses. A systematic literature review was conducted using PubMed to identify studies focusing on voriconazole therapeutic drug monitoring with data of both inflammation (assessed by C-reactive protein level) and the pharmacogenomics of cytochromes P450. Individual patient data were collected and analyzed in a mixed-effect model. In total, 203 patients and 754 voriconazole trough concentrations from six studies were included. Voriconazole trough concentrations were independently influenced by age, dose, C-reactive protein level, and both cytochrome P450 2C19 and 3A4 genotype, considered individually or through a combined genetic score. An increase in the C-reactive protein of 10, 50, or 100 mg/L was associated with an increased voriconazole trough concentration of 6, 35, or 82%, respectively. The inhibitory effect of inflammation appeared to be less important for patients with loss-of-function polymorphisms for cytochrome P450 2C19. Voriconazole exposure is influenced by age, inflammatory status, and the genotypes of both cytochromes P450 2C19 and 3A4, suggesting that all these determinants need to be considered in approaches of personalization of voriconazole treatment.


Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 4442-4451
Author(s):  
Sagheer Ahmed ◽  
Saima Gul ◽  
Muhammad Akhlaq ◽  
Abrar Hussain ◽  
Sidrah Tariq Khan ◽  
...  

Medicine ◽  
2020 ◽  
Vol 99 (50) ◽  
pp. e23652
Author(s):  
Yongxin Yang ◽  
Yaping Zhang ◽  
Ming Ren ◽  
Yonglan Wang ◽  
Zhuoma Cairang ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Domenico G Della Rocca ◽  
Rodney Horton ◽  
Carola Gianni ◽  
Luigi Di Biase ◽  
CHINTAN G TRIVEDI ◽  
...  

Introduction: Loss-of-function (LOF) polymorphisms of the cytochrome P450 2C19 (CYP2C19) gene are associated with reduced hepatic bioactivation of clopidogrel. Hypothesis: To evaluate the prevalence of LOF polymorphisms of CYP2C19 and the incidence of device-related thrombosis (DRT) when clopidogrel is replaced with half dose novel oral anticoagulant (NOAC) in patients with reduced clopidogrel metabolism. Methods: Consecutive Watchman patients were genotyped for CYP2C19 polymorphisms. Patients with reduced clopidogrel metabolism received half dose NOAC plus aspirin during the “dual antiplatelet therapy (DAPT) phase” post-Watchman implantation (between 45 days and 6 months). The incidence of DRT among genotyped patients (Group I, n=401) and a control group without genotypization (Group II, n=357) which received standard DAPT is reported. Results: Overall, 758 Watchman patients were included (mean age: 75±8 yrs, 63% males, CHA 2 DS 2 -VASc: 4.6±1.5; HAS-BLED: 3.2±1.1). Of the 401 Group 1 patients, 25.69% (n=103) were reduced clopidogrel metabolizers. In 87.4% of them, clopidogrel was replaced with half-dose NOAC during the “DAPT phase” post-Watchman implantation whereas 12.6% received ASA plus full-dose NOAC due to the presence of a significant peri-device leak. During the “DAPT phase”, DRT was documented in 1 (0.2%) patient of Group I and 7 (1.96%) patients of Group II (p=0.029). On multivariate analysis, a genotype-tailored antithrombotic strategy was associated with a significant reduction in DRT (odds ratio: 0.11; 95% confidence interval: 0.01 - 0.98; p-value: 0.048). Conclusions: Approximately 25% of our Watchman patients had clopidogrel resistance. Substitution of clopidogrel with half dose NOAC in reduced clopidogrel metabolizers significantly reduced the incidence of DRT.


2020 ◽  
Vol 76 (5) ◽  
pp. 479-486
Author(s):  
Takashi Ishimatsu ◽  
Ken-ichiro Sasaki ◽  
Tatsuyuki Kakuma ◽  
Atsushi Harada ◽  
Yuji Hirakawa ◽  
...  

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e038031
Author(s):  
Tae-Jin Song ◽  
Jinkwon Kim ◽  
Sang Won Han ◽  
Young Dae Kim ◽  
Jong Yun Lee ◽  
...  

IntroductionClopidogrel is an antiplatelet agent that is widely used for the secondary prevention of cardiovascular and cerebrovascular events. The genotype of cytochrome P450 2C19 (CYP2C19) differentially affects the liver’s metabolism of clopidogrel, which may influence the drug’s response and efficacy for cardiovascular event prevention. In contrast to prior studies of patients with coronary artery diseases, little is known about whether the CYP2C19 genotype influences the preventive efficacy of clopidogrel in patients who had a stroke. We hypothesise that, among patients who had an acute ischaemic stroke who are prescribed clopidogrel, the patients with a loss-of-function CYP2C19 genotype (poor and intermediate metabolisers) may be at a higher risk of composite cardiovascular events than those who are non-carriers (extensive metabolisers).Methods and analysisThis prospective observational multicentre study was designed to determine whether composite cardiovascular events would differ among patients who had an ischaemic stroke prescribed clopidogrel according to CYP2C19 genotype (poor or intermediate vs extensive metabolisers). Inclusion criteria were patients who had an acute ischaemic stroke who underwent CYP2C19 genotype evaluation and received clopidogrel within 72 hours of stroke onset. The primary outcome is composite cardiovascular events (stroke, myocardial infarction, or cardiovascular death) within 6 months after acute ischaemic stroke between patients categorised as poor or intermediate metabolisers and those categorised as extensive metabolisers according to their CYP2C19 genotype.Ethics and disseminationThe Institutional Review Board of Severance Hospital, Yonsei University College of Medicine approved this study (3-2019-0195). We received study approval from the institutional review board of each participating hospital. We plan to disseminate our findings at relevant conferences and meetings and through peer-reviewed journals.Trial registration numberNCT04072705.


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