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A F Favela-Mendoza, G Martínez-Cortes, M M Romero-Prado, E M Romero-Tejeda, M C Islas-Carbajal, M Sosa-Macias, I Lares-Asseff, H Rangel-Villalobos
WHAT IS KNOWN AND OBJECTIVE: CYP2C19 genotypes presumably allow the prediction of the metabolizer phenotypes: poor (PMs), extensive (EMs) and ultra-rapid (UMs). However, evidence from previous studies regarding this predictive power is unclear, which is important because the benefits expected by healthcare institutions and patients are based on this premise. Therefore, we aimed to complete a formal evaluation of the diagnostic value of CYP2C19 and CYP3A4 genes for predicting metabolizer phenotypes established by omeprazole (OME) administration in 118 healthy children from Jalisco (western Mexico)...
May 7, 2018: Journal of Clinical Pharmacy and Therapeutics
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 the 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 ultrarapid (UM); inferred from *2, *3, and *17 allele determination). From 123 patients, IM-PM had a 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
Ramón Cacabelos, Arun Meyyazhagan, Juan C Carril, Pablo Cacabelos, Óscar Teijido
Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products...
January 3, 2018: Journal of Personalized Medicine
Lana Ganoci, Tamara Božina, Nikica Mirošević Skvrce, Mila Lovrić, Petar Mas, Nada Božina
BACKGROUND: Data on the frequency of pharmacogenetic polymorphisms in the Croatian population are limited. We determined and analyzed frequencies for the most important CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 genetic variants in the Croatian population. METHODS: 2637 subjects were included. Genotyping was performed by real-time polymerase chain reaction (PCR) using TaqMan® DME or TaqMan® SNP Genotyping Assays, and by PCR, and PCR-RFLP analysis. RESULTS: For CYP2C9, allele frequencies of *2 and *3 variant were 14...
February 11, 2017: Drug Metabolism and Personalized Therapy
Issam S Hamadeh, Kenneth P Klinker, Samuel J Borgert, Ashley I Richards, Wenhui Li, Naveen Mangal, John W Hiemenz, Stephan Schmidt, Taimour Y Langaee, Charles A Peloquin, Julie A Johnson, Larisa H Cavallari
OBJECTIVES: Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2C19 genotype and subtherapeutic voriconazole concentrations in adults with IFIs. PATIENT AND METHODS: Adults receiving weight-based voriconazole dosing for the treatment of IFIs were genotyped for the CYP2C19*2, *3, and *17 polymorphisms, and CYP2C19 metabolizer phenotypes were inferred...
May 2017: Pharmacogenetics and Genomics
Lana Ganoci, Tamara Božina, Nikica Mirošević Skvrce, Mila Lovrić, Petar Mas, Nada Božina
BACKGROUND: Data on the frequency of pharmacogenetic polymorphisms in the Croatian population are limited. We determined and analyzed frequencies for the most important CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 genetic variants in the Croatian population. METHODS: 2637 subjects were included. Genotyping was performed by real-time polymerase chain reaction (PCR) using TaqMan® DME or TaqMan® SNP Genotyping Assays, and by PCR, and PCR-RFLP analysis. RESULTS: For CYP2C9, allele frequencies of *2 and *3 variant were 14...
March 1, 2017: Drug Metabolism and Personalized Therapy
Jae-Lim Choi, Bo-Ram Kim, Kwang-Sook Woo, Kyeong-Hee Kim, Jeong-Man Kim, Moo-Hyun Kim, Jin-Yeong Han
BACKGROUND: Clopidogrel is a widely used antiplatelet agent for dual antiplatelet therapy and metabolized by CYP2C19. The polymorphism of CYP2C19 is associated with the therapeutic effect of clopidogrel. METHODS: A total of 119 patients diagnosed with acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) with drug-eluting stents was enrolled. Polymorphisms of CYP2C19 *2,*3,*17 were determined by the Spartan RX CYP2C19 and confirmed by SNP genotyping assay...
September 2016: Annals of Clinical and Laboratory Science
J A Trubiano, A Crowe, L J Worth, K A Thursky, M A Slavin
OBJECTIVES: The clinical utility of pharmacogenomic testing in haematology patients with invasive fungal disease (IFD) receiving azole therapy has not been defined. We report our experience with CYP2C19 testing in haematological patients requiring voriconazole therapy for IFD. METHODS: As a single-centre pilot study, 19 consecutive patients with a haematological malignancy undergoing active chemotherapy with a possible, probable or proven IFD requiring voriconazole therapy underwent CYP2C19 testing from 2013 to 2014...
April 2015: Journal of Antimicrobial Chemotherapy
Chanagune Srinarong, Sith Siramolpiwat, Arti Wongcha-um, Varocha Mahachai, Ratha-korn Vilaichone
BACKGROUND: Helicobacter pylori (H. pylori) remains an important cause of gastric cancer and peptic ulcer disease worldwide. Treatment of H. pylori infection is one of the effective ways to prevent gastric cancer. However, standard triple therapy for H. pylori eradication is no longer effective in many countries, including Thailand. This study was designed to evaluate the efficacy of adding bismuth and probiotic to standard triple therapy for H. pylori eradication. MATERIALS AND METHODS: In this prospective single center study, H...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
Edoardo Spina, Jose de Leon
A critical review of the limited available evidence and the authors' experience and judgment are used to summarize the role of cytochrome P450 (CYP) genetic variants in the pharmacokinetics of and clinical response to psychotropic medications. CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 genetic polymorphisms and their contributions to the metabolism of psychotropic drugs are reviewed. CYP1A2, CYP2B6 and CYP3A4 genotyping have limited current clinical utility. CYP2C9 genotyping has no utility in psychiatry...
January 2015: Journal of Neural Transmission
Ming Chang, Gunnel Tybring, Marja-Liisa Dahl, Jonatan D Lindh
BACKGROUND: Citalopram and escitalopram, selective serotonin reuptake inhibitors, are primarily metabolized by cytochrome P450 (CYP) 2C19, which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics. However, the impact of CYP2C19 polymorphisms on citalopram or escitalopram exposure has yet to be fully clarified, especially with regard to the quantitative impact of the CYP2C19*17 allele. OBJECTIVE: The objective of this study was to quantify the effect of functional CYP2C19 allele variants on citalopram/escitalopram exposure...
September 2014: Clinical Pharmacokinetics
Koji Chiba, Keiko Shimizu, Motohiro Kato, Takaaki Nishibayashi, Kazuki Terada, Nobuo Izumo, Yuichi Sugiyama
Significant inter-individual variability of exposure for CYP2C19 substrates may be only partly due to genetic polymorphism. Therefore, the in vivo inter-individual variability in hepatic intrinsic clearance (CL(int,h)) of CYP2C19 substrates was estimated from reported AUC values using Monte Carlo simulations. The coefficient of variation (CV) for CL(int,h) in poor metabolizers (PM) expected from genotypes CYP2C19*2/*2, CYP2C19*3/*3 or CYP2C19*2/*3 was estimated as 25.8% from the CV for AUC of omeprazole in PMs...
2014: Drug Metabolism and Pharmacokinetics
Hyunjung Kim, Yonggoo Kim, Yoon-Seok Koh, Hae Kyung Lee, Hyojin Chae, Dong Wook Jekarl, Jong-Min Lee, Woo-Seung Shin, Tae-Hoon Kim
The purpose of this study was to evaluate associations between INNOVANCE PFA P2Y (PFA P2Y) test results and CYP2C19 genotypes and provide baseline data for PFA P2Y testing to establish a therapeutic monitoring strategy for clopidogrel. A total of 75 new patients with acute coronary syndrome with planned percutaneous coronary intervention were enrolled between June 2012 and September 2012. All patients received clopidogrel at an initial loading dose of 600 mg followed by a 75-mg daily maintenance dose. Blood samples were obtained on the third morning after clopidogrel loading...
2015: Platelets
Leena H Saeed, Ahmed Y Mayet
UNLABELLED: CYP2C19 is a cytochrome P450 enzyme, which is involved in the metabolism of some clinically important medications and is encoded by a highly polymorphic gene. There is no available data on the distribution of the CYP2C19 *4 and *17 mutant alleles in the Saudi Arabian population. The aim of the study was to determine different CYP2C19 mutant allele (*2, *4 and *17) frequencies in healthy Saudi subjects and to determine genotype frequencies for these mutations. The CYP2C19 genotypes were then classified into phenotypes...
2013: International Journal of Medical Sciences
Oscar Ö Braun, Dominick J Angiolillo, Jose L Ferreiro, Joseph A Jakubowski, Kenneth J Winters, Mark B Effron, Suman Duvvuru, Timothy M Costigan, Scott Sundseth, Joseph R Walker, Jorge F Saucedo, Neal S Kleiman, Christoph Varenhorst
Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers)...
December 2013: Thrombosis and Haemostasis
C F Samer, K Ing Lorenzini, V Rollason, Y Daali, J A Desmeules
Interindividual variability in drug response is a major clinical problem. Polymedication and genetic polymorphisms modulating drug-metabolising enzyme activities (cytochromes P450, CYP) are identified sources of variability in drug responses. We present here the relevant data on the clinical impact of the major CYP polymorphisms (CYP2D6, CYP2C19 and CYP2C9) on drug therapy where genotyping and phenotyping may be considered, and the guidelines developed when available. CYP2D6 is responsible for the oxidative metabolism of up to 25% of commonly prescribed drugs such as antidepressants, antipsychotics, opioids, antiarrythmics and tamoxifen...
June 2013: Molecular Diagnosis & Therapy
Jin Joo Park, Kyung Woo Park, Jeehoon Kang, Ki-Hyun Jeon, Si-Hyuck Kang, Hyo Suk Ahn, Jung-Kyu Han, Jin-Sin Koh, Sang Eun Lee, Han-Mo Yang, Hae-Young Lee, Hyun-Jae Kang, Bon-Kwon Koo, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
BACKGROUND: Variations of genes encoding cytochrome enzymes, drug transporters, and paraoxonase have recently been reported to be associated with clopidogrel response variability besides the well-known CYP2C19 loss-of-function (LOF) alleles. We determined whether newly reported genetic variations are associated with clopidogrel on-treatment platelet reactivity (OPR) in Korean patients. METHODS: OPR was measured in 1264 consecutive patients who underwent percutaneous coronary intervention using the VerifyNowP2Y12 assay system and genotyping of PON-1 Q192R, ABCB1 C3435T, CYP1A2*1F, CYP2B6*6, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP3A4 (IVS10+12G>A), and CYP3A5*3 was performed...
February 10, 2013: International Journal of Cardiology
Daniel J Müller, Eva J Brandl, Rudi Hwang, Arun K Tiwari, Jessica E Sturgess, Clement C Zai, Jeffrey A Lieberman, James L Kennedy, Margaret A Richter
AIM: Genetic factors can result in variance in drug metabolism enzyme function, which is one major mechanism impacting on interindividual variability in response and side effects. We therefore performed a pilot study to investigate genetic variants in the drug metabolizing enzymes CYP2D6 and CYP2C19. METHODS: We evaluated 35 schizophrenic and 39 obsessive compulsive disorder (OCD) patients treated with various antipsychotics and antidepressants. Patients were assessed for treatment response and side effects...
August 2012: Genetic Testing and Molecular Biomarkers
Xavier Boulenc, Nassim Djebli, Juan Shi, Laurent Perrin, William Brian, Robert Van Horn, Fabrice Hurbin
Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to active metabolite formation. In the current study, net CYP2C19 contribution to the active metabolite formation was determined from exposure of the active metabolite in two clinical studies (one phase I study with well balanced genetic polymorphic populations and a meta-analysis with a total of 396 healthy volunteers) at different clopidogrel doses...
January 2012: Drug Metabolism and Disposition: the Biological Fate of Chemicals
J J Swen, T van der Straaten, J A M Wessels, M L Bouvy, E E W Vlassak, W J J Assendelft, H-J Guchelaar
PURPOSE: Our purpose was to investigate the feasibility of pharmacy-initiated pharmacogenetic (PGt) screening in primary care with respect to patient willingness to participate, quality of DNA collection with saliva kits, genotyping, and dispensing data retrieved from the pharmacy. METHODS: Polypharmacy patients aged >60 years who used at least one drug with Anatomical Therapeutic Chemical (ATC) code N06AA01-N06AX19 (antidepressants), A02BC01-A02BC05 (proton-pump inhibitors), N05AA01-N05AH04 (antipsychotics), or C07AB02 (metoprolol) in the preceding 2 years were randomly selected...
April 2012: European Journal of Clinical Pharmacology
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