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https://www.readbyqxmd.com/read/28723731/the-combined-effect-of-cyp2b6-genotype-and-other-candidate-genes-on-a-steady-state-serum-concentration-of-methadone-in-opioid-maintenance-treatment
#1
Marianne K Kringen, Fatemeh Chalabianloo, Jean-Paul Bernard, Jørgen G Bramness, Espen Molden, Gudrun Høiseth
BACKGROUND: A considerable inter-individual variability in methadone pharmacokinetics is seen in patients on methadone maintenance treatment. The aim of this study was to clarify the impact of the reduced function CYP2B6*6 variant allele together with variants in other candidate genes on a steady-state methadone concentration in a naturalistic setting. METHODS: Information of methadone serum concentration, dose, age, gender and CYP2C9, CYP2C19, and CYP2D6 genotypes were collected from a routine therapeutic drug monitoring (TDM) database while variant alleles in CYP2B6 and CYP3A5 were retrospectively genotyped...
July 18, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28707077/association-of-abcb1-promoter-methylation-with-aspirin-exposure-platelet-function-and-clinical-outcomes-in-chinese-intracranial-artery-stenosis-patients
#2
Xingang Li, Kun Zhao, Ning Ma, Shusen Sun, Zhongrong Miao, Zhigang Zhao
PURPOSE: DNA methylation typically acts to repress gene transcription. ABCB1 is involved in the intestinal absorption of aspirin. We aimed to investigate the impact of methylation status of ABCB1 promoter on aspirin exposure, platelet function, and clinical outcomes in Chinese intracranial artery stenosis patients receiving antiplatelet treatment. METHODS: Symptomatic intracranial artery stenosis patients (without carrying CYP2C19 loss-of-function alleles) receiving antiplatelet therapy were enrolled in this study...
July 13, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28699807/personalizing-antiplatelet-prescribing-using-genetics-for-patients-undergoing-percutaneous-coronary-intervention
#3
Larisa H Cavallari
Clopidogrel is commonly prescribed with aspirin to reduce the risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). However, there is significant inter-patient variability in clopidogrel response. The CYP2C19 enzyme is involved in the biotransformation of clopidogrel to its pharmacologically active form, and variation in the CYP2C19 gene contributes to clopidogrel response variability. Areas covered. This article describes the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics, and effectiveness...
July 12, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28690699/feasibility-of-clinical-pharmacist-led-cyp2c19-genotyping-for-patients-receiving-non-emergent-cardiac-catheterization-in-an-integrated-health-system
#4
Samuel G Johnson, Paul B Shaw, Thomas Delate, Deanna L Kurz, Dylon Gregg, John C Darnell, Christina L Aquilante
OBJECTIVE: To assess the feasibility of clinical pharmacist-led CYP2C19 genotype-guided P2Y12 inhibitor antiplatelet drug therapy recommendations to cardiologists in an outpatient cardiology practice. METHODS: This was a prospective, open-labeled, single-arm study conducted in an integrated healthcare delivery system between March 1, 2013 and January 23, 2014. Patients requiring non-emergent cardiac catheterization were included. A clinical pharmacist provided interpretation and recommendations from genotyping results...
April 2017: Pharmacy Practice
https://www.readbyqxmd.com/read/28689434/role-of-genetic-testing-in-patients-undergoing-percutaneous-coronary-intervention
#5
Jae Youn Moon, Francesco Franchi, Fabiana Rollini, Jose R Rivas Rios, Megha Kureti, Larisa H Cavallari, Dominick J Angiolillo
Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor)...
July 10, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28687336/polymorphisms-of-cyp2c8-cyp2c9-and-cyp2c19-and-risk-of-coronary-heart-disease-in-russian-population
#6
Alexey Polonikov, Alexander Kharchenko, Marina Bykanova, Svetlana Sirotina, Irina Ponomarenko, Anna Bocharova, Kseniya Vagaytseva, Vadim Stepanov, Olga Bushueva, Mikhail Churnosov, Maria Solodilova
Epoxyeicosatrienoic acids (EETs) are important vasoactive products of arachidonic acid metabolism with a wide range of biological actions in the cardiovascular system. The present study investigated whether single nucleotide polymorphisms (SNP) of genes coding cytochrome P450 2C subfamily, enzymes involved in biosynthesis of EETs, are associated with the risk of coronary heart disease (CHD). A total of 1255 unrelated Russian subjects comprising 561 patients with angiographically diagnosed CHD and 694 age- and sex-matched healthy subjects were included in the study...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28685218/influence-of-cyp2c19-genotypes-on-the-occurrence-of-adverse-drug-reactions-of-voriconazole-among-hematological-patients-after-allo-hsct
#7
Beata Sienkiewicz, Donata Urbaniak-Kujda, Jarosław Dybko, Andrzej Dryś, Magdalena Hurkacz, Tomasz Wróbel, Anna Wiela-Hojeńska
The aim of this study was to determine the influence of different CYP2C19 genotypes on selected liver function parameters, and ADR occurrence during VCZ prophylaxis in adult patients after allo-HSCT (allogeneic hematopoietic stem cell transplantation). CYP2C19 mutations were determined in a cohort of 30 adults using PCR-RFLP methods established by Sim et al. and Goldstein and Blaisdell. The patients' protocol included biometrical and biochemical data, information on the underlying disease, chemotherapy, molds infections occurring during VCZ treatment, adverse drug reactions typical for the use of voriconazole, and probable drug - drug interactions...
July 6, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28681220/comparison-of-platelet-aggregation-response-in-switching-regimen-from-prasugrel-to-clopidogrel-between-cyp2c19-extensive-versus-non-extensive-metabolizers
#8
Soichiro Ebisawa, Yasushi Ueki, Tomoaki Mochidome, Keisuke Senda, Hitoshi Nishimura, Tatsuya Saigusa, Takashi Miura, Hirohiko Motoki, Jun Koyama, Uichi Ikeda
Little is known about the response of platelet aggregation in patients with acute coronary syndrome (ACS) when prasugrel is changed to clopidogrel. In this study, we evaluated the pharmacodynamic effects of this medication switch. Twenty-one consecutive ACS patients received prasugrel 20 mg as a loading dose before emergent percutaneous coronary intervention and 3.75 mg as a maintenance dose on days 2-7 (prasugrel phase). From day 8, prasugrel was switched to clopidogrel 75 mg/day (clopidogrel phase). P2Y12 reaction units (PRU) were measured 2-4 h after prasugrel loading, and on days 7, 11, 13, 15, and 42...
July 5, 2017: Cardiovascular Intervention and Therapeutics
https://www.readbyqxmd.com/read/28679023/notable-drug-drug-interaction-between-etizolam-and-itraconazole-in-poor-metabolizers-of-cytochrome-p450-2c19
#9
Takehito Yamamoto, Kenichi Furihata, Akihiro Hisaka, Takashi Moritoyo, Kazuaki Ogoe, Shizuko Kusayama, Keiju Motohashi, Akiko Mori, Takeshi Iwatsubo, Hiroshi Suzuki
In this study, impact of a polymorphism of CYP2C19 on drug-drug interaction (DDI) was examined for etizolam. The effect of itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics of etizolam (a substrate of CYP2C19 and CYP3A) was assessed in both extensive metabolizers (EMs) and poor metabolizers (PMs) of CYP2C19. Sixteen participants (8 EMs and 8 PMs) received a single oral dose of etizolam (0.25 mg) on day 1. The participants ingested itraconazole (200 mg twice a day) on days 2-5. On day 5, participants received an oral dose of etizolam (0...
July 5, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28674348/randomized-trial-comparing-esomeprazole-and-rabeprazole-in-first-line-eradication-therapy-for-helicobacter-pylori-infection-based-on-the-serum-levels-of-pepsinogens
#10
Tadashi Shimoyama, Daisuke Chinda, Yoshihiko Sawada, Kazuo Komai, Hironobu Chiba, Yoshiharu Saito, Yoshio Sasaki, Masashi Matsuzaka, Shinsaku Fukuda
Objective CYP2C19 metabolic activity influences the efficacy of Helicobacter pylori eradication therapies comprising PPIs. Rabeprazole (RPZ) and esomeprazole (EPZ) are PPIs not extensively metabolized by CYP2C19. The aim of this study was to elucidate whether or not first-line triple therapies using RPZ or EPZ are equally effective in Japanese patients with different CYP2C19 genotypes. Methods Two-hundred patients infected with H. pylori were randomized to receive one of the following regimens: amoxicillin (750 mg), clarithromycin (200 mg), and either esomeprazole (20 mg) (EAC group) or rabeprazole (10 mg) (RAC group), twice a day for one week...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28664816/cyp2c19-17-protects-against-metabolic-complications-of-clozapine-treatment
#11
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Micheline Coelho, Trudi Jones, Tristan Nguyen, Steven Boyages, Mark McLean
OBJECTIVES: Clozapine (CZ) is the most effective drug for managing treatment-resistant schizophrenic disorders. Its use has been limited due to adverse effects, which include weight gain and new-onset diabetes, but the incidence of these varies between patients. METHODS: We investigated 187 Clozapine Clinic patients (of whom 137 consented for genotyping) for the presence of CYP2C19*17 and its association with CZ and NCZ levels, and clinical outcomes. RESULTS: Thirty-nine percent of genotyped patients were carriers of the CYP2C 19*17 polymorphism...
June 30, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28664594/evaluation-of-baseline-frequency-of-sister-chromatid-exchanges-in-an-italian-population-according-to-age-sex-smoking-habits-and-gene-polymorphisms
#12
Alfredo Santovito, Claudio Gendusa, Piero Cervella
OBJECTIVES: Increased SCEs frequencies in human lymphocytes are an indicator of spontaneous chromosome instability and could be influenced by different exogenous and endogenous factors. In this study, we evaluated the influence of age, sex, smoking habits, and genetic polymorphisms on the background levels of SCEs in peripheral blood lymphocytes. METHODS: Two hundred-thirty healthy Italian subjects were recruited. Data about age, sex and smoking habits were recorded...
June 30, 2017: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/28662503/the-effects-of-switching-to-vonoprazan-a-novel-potassium-competitive-acid-blocker-on-gastric-acidity-and-reflux-patterns-in-patients-with-erosive-esophagitis-refractory-to-proton-pump-inhibitors
#13
Hiroshi Yamashita, Atsushi Kanamori, Chise Kano, Hiroki Hashimura, Kei Matsumoto, Masahiro Tsujimae, Tetsuya Yoshizaki, Kenji Momose, Daisuke Obata, Takaaki Eguchi, Mikio Fujita, Akihiko Okada
BACKGROUND/AIM: The effects of vonoprazan and proton pump inhibitors (PPIs) in patients with reflux esophagitis (RE) have not yet been compared using multichannel intraluminal impedance-pH (MII-pH). METHODS: A total of 8 patients with persistent gastric mucosal injury, despite completing an 8-week standard PPI therapy, were enrolled in the study. While they were on standard PPI therapy, the baseline values of reflux parameters, holding time ratio (HTR) of gastric pH >4, and esophageal pH <4 were obtained by using 24 h MII-pH monitoring...
June 30, 2017: Digestion
https://www.readbyqxmd.com/read/28657402/in-vitro-evaluation-of-the-inhibition-and-induction-potential-of-olaparib-a-potent-poly-adp-ribose-polymerase-inhibitor-on-cytochrome-p450
#14
Alex McCormick, Helen Swaisland, Venkatesh Pilla Reddy, Maria Learoyd, Graeme Scarfe
1. In vitro studies were conducted to evaluate potential inhibitory and inductive effects of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, on cytochrome P450 (CYP) enzymes. Inhibitory effects were determined in human liver microsomes (HLM); inductive effects were evaluated in cultured human hepatocytes. 2. Olaparib did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2D6 or CYP2E1 and caused slight inhibition of CYP2C9, CYP2C19 and CYP3A4/5 in HLM up to a concentration of 100 µM. However, olaparib (17‒500 µM) inhibited CYP3A4/5 with an IC50 of 119 µM...
June 28, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28653333/investigating-real-world-clopidogrel-pharmacogenetics-in-stroke-using-a-bioresource-linked-to-electronic-medical-records
#15
Aleksi Tornio, Rob Flynn, Steve Morant, Elena Velten, Colin N A Palmer, Thomas M MacDonald, Alex S F Doney
Clopidogrel efficacy is influenced by genetic variation of CYP2C19, however few studies have considered stroke patients. We used electronic medical records (EMR) linked to a bioresource to examine real-world implications of clopidogrel pharmacogenetics in stroke. Patients hospitalized for any arterial thrombo-occlusive event (ATO) who subsequently redeemed clopidogrel prescriptions in the community were entered into the study (n=651). During 24 months follow-up the primary endpoint of recurrent ATO or death occurred in 299 (46%) patients...
June 27, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28639488/prenatal-exposure-to-serotonin-reuptake-inhibitors-and-congenital-heart-anomalies-an-exploratory-pharmacogenetics-study
#16
Aizati N A Daud, Jorieke E H Bergman, Wilhelmina S Kerstjens-Frederikse, Pieter van der Vlies, Eelko Hak, Rolf M F Berger, Henk Groen, Bob Wilffert
AIM: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors. METHODS: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B. RESULTS: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28639468/cyp2d6-and-cyp2c19-genotyping-in-psychiatric-patients-on-psychotropic-medication-in-the-former-dutch-antilles
#17
Anne B Koopmans, David J Vinkers, Petra Ja Gelan, Hans W Hoek, Peter N van Harten
AIM: This study was aimed to asses the prevalence of CYP2D6 and CYP2C19 polymorphisms in psychiatric patients and in volunteers from Dutch caribbean origin. METHODS: In total, 435 individuals were genotyped for CYP2D6 and CYP2C19. Of these, 269 were psychiatric patients on psychotropic medication, living in Curaçao and 166 were volunteers from the Dutch Caribbean population. RESULTS: No differences in prevalence of alleles were found. CONCLUSION: Although prevalence of alleles appeared to be very different from African and Caucasian populations, the distribution into predicted phenotypes shows an equal distribution as in Caucasians...
July 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28638276/gastric-juice-based-real-time-pcr-for-tailored-helicobacter-pylori-treatment-a-practical-approach
#18
Xianhui Peng, Zhiqiang Song, Lihua He, Sanren Lin, Yanan Gong, Lu Sun, Fei Zhao, Yixin Gu, Yuanhai You, Liya Zhou, Jianzhong Zhang
A gastric juice-based real-time polymerase chain reaction (PCR) assay was established to identify Helicobacter pylori infection, clarithromycin susceptibility and human CYP2C19 genotypes and to guide the choice of proton pump inhibitor (PPI), clarithromycin and amoxicillin treatment for tailored H. pylori eradication therapy. From January 2013 to November 2014, 178 consecutive dyspeptic patients were enrolled for collection of gastric biopsy samples and gastric juice by endoscopy at the Peking University Third Hospital; 105 and 73 H...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28631703/-association-of-itgb3-p2ry12-and-cyp2c19-gene-polymorphisms-with-platelet-functional-activity-in-patients-with-coronary-heart-disease-during-dual-antiplatelet-therapy
#19
E F Muslimova, S A Afanasiev, T Yu Rebrova, T N Sergienko, A N Repin
AIM: To assess the association of CYP2C19 G681A, P2RY12 H1/H2, and ITGB3 T1565C polymorphisms with the extent of platelet aggregation in patients with coronary heart disease (CHD) during antiplatelet therapy. SUBJECTS AND METHODS: 166 male patients with CHD, living in the Western Siberian Region, were examined. All the patients underwent a test for platelet aggregation induced by ADP (2.5 and 5.0 µm) and epinephrine (0.2 µm). Genotyping was performed using an allele-specific polymerase chain reaction technique...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28626197/evaluation-of-cyp2d6-protein-expression-and-activity-in-the-small-intestine-to-determine-its-metabolic-capability-in-the-japanese-population
#20
Momoko Kawakami, Sachiko Takenoshita-Nakaya, Yuko Takeba, Yuki Nishimura, Masayuki Oda, Minoru Watanabe, Yuki Ohta, Shinjiro Kobayashi, Takehito Ohtsubo, Shinichi Kobayashi, Naoki Uchida, Naoki Matsumoto
CYP2D6 plays an important role in the metabolism of many drugs such as opioids and antidepressants. Polymorphisms of the CYP2D6 gene are widely observed in the Japanese population, and can affect the first-pass metabolism of orally administered drugs. Several CYP enzymes have been identified in the small intestine of Caucasians, but intestinal CYP enzymes have not been reported in the Japanese population, except for CYP3A4 and CYP2C19. In this study, we evaluated the CYP2D6 metabolic capacity by measurement of CYP2D6 mRNA and protein levels and activity in the small intestine of Japanese individuals...
June 14, 2017: Biological & Pharmaceutical Bulletin
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