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H L Qu, D D Guo, T Xu, Z Li, J Yin, X P Tian, D Q Kong, X M Zhu, L Y Miao, D P Wu, X W Tang
Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Ameen M Mohammad Fic, Nasir As Al-Allawi
To determine the impact of CYP2C19 genotyping on the occurrence of major adverse cardiovascular events (MACE), in cohort of Iraqi patients on clopidogrel post percutaneous coronary intervention (PCI), a total of 201 Iraqi patients undergoing the latter procedure were enrolled. All enrollees had their CYP2C19 genotyped using PCR and reverse hybridization. Genotyping revealed that CYP2C19 *1, *17, *2 and *8 allele frequencies were respectively 0.604, 0.276, 0.117 and 0.0026. After the exclusion of those with two loss of function alleles, 186 patients were available for follow-up as long as they were on clopidogrel, or until MACE occurred, which was encountered in 8...
March 12, 2018: Journal of Cardiovascular Pharmacology
Fadzilah Adibah Abd Majid, Nur Syukriah Ab Rahman, Effendy Abd Wahid, Ain Nabihah Zainudin, Siti Nurazwa Zainol, Hassan Fahmi Ismail, Tet Soon Wong, K Vijaya Bhargava, Nirbhay Kumar Tiwari, Sanjeev Giri
Drug interaction of SynacinnTM polyherbal with known diabetic drugs is unknown. SynacinnTM contains standardized extracts of five herbal against gallic acid, curcumin, rosmarinic acid, catechin and andrographolide. SynacinnTM and its five standard markers were analysed for its possible interaction with CYP450 enzymes assay. This study was conducted using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4(Midazolam) and CYP3A4 (Testosteron)...
March 13, 2018: Drug Metabolism Letters
Francesca Maria Notarangelo, Giuseppe Maglietta, Paola Bevilacqua, Marco Cereda, Piera Angelica Merlini, Giovanni Quinto Villani, Paolo Moruzzi, Giampiero Patrizi, Guidantonio Malagoli Tagliazucchi, Antonio Crocamo, Angela Guidorossi, Filippo Pigazzani, Elisa Nicosia, Giorgia Paoli, Marco Bianchessi, Mario Angelo Comelli, Caterina Caminiti, Diego Ardissino
BACKGROUND: Clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), but its efficacy is hampered by interpatient response variability, due to genetic polymorphisms associated with clopidogrel metabolism. OBJECTIVE: To evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes in comparison with the standard of care, which bases the selection on clinical characteristics alone METHODS: Patients hospitalised for ACS were randomly assigned to standard of care or pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, CYP2C19*17 using an ST Q3 system that provide the data within 70 minutes at each patient's bedside...
February 24, 2018: Journal of the American College of Cardiology
Marjolein Drent, Petal Wijnen, Aalt Bast
PURPOSE OF REVIEW: Fibrosing interstitial pneumonias are associated with various stages of fibrosis. The cause of this group of syndromes remains largely unknown. For most of these diseases, a genetic basis, environmental factors and certain triggers have been suggested as possible risk factors. Various studies have found an association between genetic polymorphisms, or the presence of certain variant alleles, and the occurrence and/or progression of interstitial pneumonias of unknown origin...
March 13, 2018: Current Opinion in Pulmonary Medicine
Miriam Saiz-Rodríguez, Daniel Romero-Palacián, Carlos Villalobos-Vilda, José Luis Caniego, Carmen Belmonte, Dora Koller, Eduardo Bárcena, María Talegón, Francisco Abad-Santos
This observational retrospective study assessed antiplatelet response and clinical events after clopidogrel treatment in patients who underwent percutaneous neurointervention, related to CYP2C19 metabolizer status (normal (NM), intermediate/poor (IM-PM) and ultra-rapid (UM); inferred from *2, *3 and *17 allele determination). From 123 patients, IM-PM had higher aggregation value (201.1 vs 137.6 NM, 149.4 UM, p<0.05) and lower response rate (37.5% vs. 69.8% NM, 61.1% UM), along with higher treatment change rate (25% vs...
March 14, 2018: Clinical Pharmacology and Therapeutics
Z Hashemizadeh, S A Malek-Hosseini, P Badiee
Background: Patients with hepatic diseases are treated with numerous drugs metabolized by cytochrome P450. Objective: To evaluate the frequencies of CYP2C19 variant alleles (*2, *3, and *17), genotypes, and phenotypes, and the relationship between the frequency of these alleles and the underlying hepatic diseases among patients with advanced liver diseases who were candidates for liver transplantation. Methods: The Study was conducted on 120 patients suffering from various hepatic disorders, candidates for liver transplantation, and 52 healthy volunteers...
2018: International Journal of Organ Transplantation Medicine
Amelia Nathania Dong, Yan Pan, Uma Devi Palanisamy, Beow Chin Yiap, Nafees Ahemad, Chin Eng Ong
Genetic polymorphism of the cytochrome P450 (CYP) genes particularly affects CYP2D6 and CYP2C19 to a functionally relevant extent, and it is therefore crucial to elucidate the enzyme kinetic and molecular basis for altered catalytic activity of these allelic variants. This study explored the expression and function of the reported alleles CYP2D6*2, CYP2D6*10, CYP2D6*17, CYP2C19*23, CYP2C19*24, and CYP2C19*25 with respect to gene polymorphisms. Site-directed mutagenesis (SDM) was carried out to generate these six alleles...
March 10, 2018: Applied Biochemistry and Biotechnology
Ryoma Igarashi, Takamitsu Inoue, Nobuhiro Fujiyama, Norihiko Tsuchiya, Kazuyuki Numakura, Hideaki Kagaya, Mitsuru Saito, Shintaro Narita, Shigeru Satoh, Takenori Niioka, Masatomo Miura, Tomonori Habuchi
Axitinib is a potent second-line molecular-targeted agent for metastatic renal cell carcinoma (mRCC). Axitinib pharmacokinetics and its relation with genetic polymorphisms were evaluated to predict the adverse events (AEs) and efficacy of axitinib. We analyzed 46 patients with mRCC who were treated with axitinib. The plasma axitinib level was measured at 0, 2, 4, 8, and 12 h after administration (C0 , C2 , C4 , C8 , and C12 ; ng/mL) on day 7 of the treatment. Genetic polymorphisms related to axitinib pharmacokinetics, including SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2, CYP2C19, CYP3A5, and UGT1A1, were analyzed...
March 9, 2018: Medical Oncology
Yu Wu, Yilun Zhou, Yuesong Pan, Xingquan Zhao, Liping Liu, David Wang, Chunxue Wang, Hao Li, S Claiborne Johnston, Xia Meng, Yilong Wang, Yongjun Wang
Clopidogrel resistance is prevalent in chronic kidney disease (CKD) patients. Genetic polymorphism is considered to be the most important factor that influences clopidogrel resistance. Limited data exist as to the role of pharmacogenetics in prognosis of stroke patients with impaired renal function on clopidogrel. We sought to explore whether decreased kidney function alters the association between CYP2C19 genetic variants and clinical outcome in patients with minor stroke or transient ischemic attack (TIA) receiving clopidogrel therapy...
March 8, 2018: Pharmacogenomics Journal
Wenjing Xiao, Jian-Ping Guo, Chun Li, Hua Ye, Wei Wei, Yaohong Zou, Lie Dai, Zhijun Li, Miaojia Zhang, Xiangpei Li, Xiaoyan Cai, Jianhong Zhao, Youlian Wang, Yi Tao, Dongzhou Liu, Yasong Li, Min Wu, Erwei Sun, Lijun Wu, Li Luo, Rong Mu, Zhanguo Li
Iguratimod (IGU) is a novel disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). Like other DMARDs, IGU exhibited significant differences in effectiveness and safety. AIM: The aim of this study was to identify genetic predictorsof efficacyand toxicity of IGU in patients with RA. MATERIALS & METHODS: Seven SNPs from IGU-metabolizing genes were genotyped in 272 IGU-treated patients with RA. Results: ABCG2 rs2231142 A allele conferred a higher response to IGU, while NAT2 rs1495742 G carriersconferred a lower response to IGU...
March 8, 2018: Pharmacogenomics
Aleš Tomek, Václav Matʼoška, Alena Frýdmanová, Hana Magerová, Martin Šrámek, Jaroslava Paulasova-Schwabová, Tereza Růžičková, Petr Janský, Ivana Šarbochová, Ivana Hadačová, Vojtěch Kaplan, Zuzana Lacinová, Luděk Táborský, Victor Serebruany
BACKGROUND: Variable response after clopidogrel is well documented and may affect major adverse clinical events after stroke. Impact of CYP2C19 genetic polymorphisms is an established marker linked to variable response after clopidogrel. However, the association of certain genetic polymorphisms with prediction of major adverse clinical events following stroke still remains controversial, especially in Caucasians. STUDY QUESTION: The primary aim was to evaluate the impact of CYP2C19 allele *2 in heterozygote form on major adverse clinical events in Caucasian poststroke survivors treated with clopidogrel...
March 2018: American Journal of Therapeutics
Karolina Tecza, Jolanta Pamula-Pilat, Joanna Lanuszewska, Dorota Butkiewicz, Ewa Grzybowska
The differences in patients' response to the same medication, toxicity included, are one of the major problems in breast cancer treatment. Chemotherapy toxicity makes a significant clinical problem due to decreased quality of life, prolongation of treatment and reinforcement of negative emotions associated with therapy. In this study we evaluated the genetic and clinical risk factors of FAC chemotherapy-related toxicities in the group of 324 breast cancer patients. Selected genes and their polymorphisms were involved in FAC drugs transport ( ABCB1, ABCC2, ABCG2,SLC22A16 ), metabolism ( ALDH3A1, CBR1, CYP1B1, CYP2C19, DPYD, GSTM1, GSTP1, GSTT1, MTHFR,TYMS ), DNA damage recognition, repair and cell cycle control ( ATM, ERCC1, ERCC2, TP53, XRCC1 )...
February 6, 2018: Oncotarget
Chen Peng, Ying Ding, Xin Yi, Yupei Shen, Zhiqiang Dong, Limei Cao, Qiang Li, Haiyan Ren, Lin He, Daizhan Zhou, Xu Chen
PURPOSE: Ischemic stroke (IS) is one of the most common neurologic diseases and is the main cause of death and disability in the Chinese population. This retrospective cohort study was performed to elucidate the relationship between single nucleotide polymorphisms (SNPs) in cytochrome P450 genes and the therapeutic effect of atorvastatin. METHODS: A total of 192 cases of IS were enrolled in the study. All patients were treated with atorvastatin, and their lipid levels and proportions were measured...
February 27, 2018: Clinical Therapeutics
John D Davis, Ashish Bansal, David Hassman, Bolanle Akinlade, Meng Li, Zhaoyang Li, Brian Swanson, Jennifer D Hamilton, A Thomas DiCioccio
This open-label drug-drug interaction study assessed whether blockade by dupilumab of interleukin (IL)-4 and IL-13 signaling affects the pharmacokinetics of drugs metabolized by cytochrome P450 (CYP450) enzymes. The pharmacokinetics of five CYP450 substrates given orally (midazolam, omeprazole, S-warfarin, caffeine, and metoprolol, metabolized by CYP3A, CYP2C19, CYP2C9, CYP1A2 and CYP2D6, respectively) were evaluated before and 28 days after initiation of dupilumab treatment (subcutaneous 300 mg weekly) in 14 patients with moderate-to-severe atopic dermatitis...
March 2, 2018: Clinical Pharmacology and Therapeutics
Fawzy Elbarbry, Aimy Ung, Khaled Abdelkawy
Background: Quercetin (QR) and thymoquinone (TQ) are herbal remedies that are currently extensively used by the general population to prevent and treat various chronic conditions. Therefore, investigating the potential of pharmacokinetic interactions caused by the concomitant use of these herbal remedies and conventional medicine is warranted to ensure patient safety. Purpose of the Study: This study was conducted to determine the inhibitory effect of QR and TQ, two commonly used remedies, on the activities of selected cytochrome P450 (CYP) enzymes that play an important role in drug metabolism and/or toxicology...
January 2018: Pharmacognosy Magazine
Ferdous A Jabir, Wisam H Hoidy
BACKGROUND: Breast cancer is the most common cancer in women characterized by a high variable clinical outcome among individuals treated with targeted therapies. PATIENTS AND METHODS: In this study, we performed a population-based approach intersecting high-throughput genotype data from Iraqi populations with publicly available pharmacogenomics information to estimate the frequency of genotypes correlated with responsiveness to breast cancer treatment thus improving the clinical management of this disease in an efficient and cost effective way...
January 31, 2018: Clinical Breast Cancer
Kanakaiah Thota, K Prasad, Mandava V Basaveswara Rao
Background: Breast cancer is the most common cancer among women worldwide. Tamoxifen (TAM), a selective estrogen receptor modulator, is widely used in its treatment. TAM is metabolized by cytochrome P450 (CYP450) enzymes, including CYP2D6, CYP3A5 and CYP2C19, whose genetic variations may have clinicopathological importance. However, reports on the association of various P450 polymorphisms with certain cancers are contradictory. Methods: We here investigated whether the prevalence of the four most common polymorphism in the CYP2D6*4 (G1934A), CYP2D6*10 (C188T), CYP3A5*3 and CYP2C19*2 alleles has any link with breast cancer using genomic DNA and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Xiangkun Wang, Tingdong Yu, Xiwen Liao, Chengkun Yang, Chuangye Han, Guangzhi Zhu, Ketuan Huang, Long Yu, Wei Qin, Hao Su, Xiaoguang Liu, Tao Peng
Cytochrome P2C (CYP2C) subfamily members (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) are known to participate in clinical drug metabolism. However, the association between CYP2C subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP2C subfamily gene expression levels with HCC prognosis. Data of 360 HCC patients in The Cancer Genome Atlas database and 231 in the Gene Expression Omnibus database were analyzed. Kaplan-Meier analysis and a Cox regression model were used to ascertain overall survival and recurrence-free survival, and to calculate median survival time using hazard ratios (HR) and 95% confidence intervals (CI)...
February 26, 2018: Cancer Medicine
Tian-Yuan Xiong, Yan-Biao Liao, Yuan Feng, Ming-Yue Zhao, Zhen-Gang Zhao, Yi-Jian Li, Xiao-Jing Liu, Mao Chen
The imaging finding of hypo-attenuated leaflet thickening (HALT) on bioprosthesis after transcatheter aortic valve replacement (TAVR) has been reported. The underlying mechanism is not clear, but leaflet thrombosis is speculated to be the cause. Heterogeneous antiplatelet responses may play a role in the process. This is a prospective, single-center pilot study in patients who received successful TAVR from June 2012 to November 2016. HALT on post-procedural multi-detector computed tomography. We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance...
February 24, 2018: Journal of Thrombosis and Thrombolysis
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