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tacrolimus pharmacogenomics

G N Almeida-Paulo, I Dapía García, R Lubomirov, A M Borobia, N L Alonso-Sánchez, L Espinosa, A J Carcas-Sansuán
Tacrolimus (TAC) is highly effective for the prevention of acute organ rejection. However, its clinical use may be challenging due to its large interindividual pharmacokinetic variability, which can be partially explained by genetic variations in TAC-metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of genetic and clinical factors on TAC pharmacokinetic variability in 21 stable pediatric renal transplant patients. This study was nested in a previous Prograf to Advagraf conversion clinical trial...
January 17, 2017: Pharmacogenomics Journal
Y Choi, F Jiang, H An, H J Park, J H Choi, H Lee
No abstract text is available yet for this article.
December 13, 2016: Pharmacogenomics Journal
T Vanhove, P Annaert, D Lambrechts, D R J Kuypers
The relevance of most genetic polymorphisms beyond CYP3A5*1 on tacrolimus disposition remains unclear. We constructed a predictive mixed model for tacrolimus dose-corrected trough concentration (C0/dose) at months 3, 12 and 24 after transplantation in a retrospective cohort of 766 predominantly Causasian adult renal recipients (n=2042 trough concentrations). All patients were genotyped for 32 single-nucleotide polymorphisms with a proven or possible relevance to tacrolimus disposition based on the previous studies...
July 5, 2016: Pharmacogenomics Journal
Y Choi, F Jiang, H An, H J Park, J H Choi, H Lee
Genetic association studies on the pharmacokinetics of tacrolimus have reported conflicting results, except for the role of the CYP3A5*3 polymorphism. The objective of this study was to identify genetic variants affecting the pharmacokinetics of tacrolimus using the DMET(TM) Plus microarray in 42 healthy males. Aside from CYP3A5*3, the rs3814055 polymorphism in the NR1I2 gene was associated with the tacrolimus pharmacokinetics based on false discovery rate-corrected multiple tests and the least absolute shrinkage and selection operator analysis...
February 16, 2016: Pharmacogenomics Journal
Rachid Abaji, Maja Krajinovic
No abstract text is available yet for this article.
2016: Expert Opinion on Drug Metabolism & Toxicology
L Quteineh, P-Y Bochud, D Golshayan, S Crettol, J-P Venetz, O Manuel, Z Kutalik, A Treyer, R Lehmann, N J Mueller, I Binet, C van Delden, J Steiger, P Mohacsi, J-F Dufour, P M Soccal, M Pascual, C B Eap
Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested...
December 8, 2015: Pharmacogenomics Journal
Lori Millner, Cesar Rodriguez, Saeed A Jortani
BACKGROUND: Unexpected clinical laboratory concentrations often need to be investigated before they are acted upon in a clinical setting. Therapeutic drug monitoring (TDM) frequently involves drugs with narrow therapeutic windows and can be harmful to the patient if changes are made based on erroneous serum drug concentrations. Too little of the drug will result in ineffective therapy and too much of the drug can cause life threatening toxicities. There are many factors that can result in unexpected serum drug concentrations including differences in analytical methods being used, diet, timing of blood draw, genotype and compliance...
October 23, 2015: Clinica Chimica Acta; International Journal of Clinical Chemistry
Wen-ying Shu, Jia-li Li, Xue-ding Wang, Min Huang
The field of pharmacogenomics was initiated in the 1950s and began to thrive after the completion of the human genome project 10 years ago. Thus far, more than 100 drug labels and clinical guidelines referring to pharmacogenomic biomarkers have been published, and several key pharmacogenomic markers for either drug safety or efficacy have been identified and subsequently adopted in clinical practice as pre-treatment genetic tests. However, a tremendous variation of genetic backgrounds exists between different ethnic groups...
May 2015: Acta Pharmacologica Sinica
Sara L Van Driest, Steven A Webber
No abstract text is available yet for this article.
February 3, 2015: Circulation
Shigeru Satoh, Takenori Niioka, Hideaki Kagaya, Kazuyuki Numakura, Takamitsu Inoue, Mitsuru Saito, Naoki Komine, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi, Masatomo Miura
UNLABELLED: Aim & patients & methods: This study investigated 24-h pharmacokinetic and CYP3A5 pharmacogenetic differences between once-daily tacrolimus (Tac-q.d.) versus twice-daily tacrolimus (Tac-b.i.d.) pretransplantation and at 1 month and 1 year post-transplantaion. RESULTS: The dose-adjusted trough level (Cmin) and area under the blood concentration-time curve from 0 to 24 h (AUC₀₋₂₄) increased twofold within 1 year post-transplantation with both formulations and the two genotypes...
August 2014: Pharmacogenomics
Kelly Birdwell
PURPOSE OF REVIEW: Pharmacogenomics is the study of differences in drug response on the basis of individual genetic background. With rapidly advancing genomic technologies and decreased costs of genotyping, the field of pharmacogenomics continues to develop. Application to patients with kidney disease provides growing opportunities for improving drug therapy. RECENT FINDINGS: Pharmacogenomics studies are lacking in patients with chronic kidney disease and dialysis, but are abundant in the kidney transplant field...
November 2014: Current Opinion in Nephrology and Hypertension
Guilherme Suarez-Kurtz, Daniela Polessa Paula, Claudio J Struchiner
The heterogeneous Brazilian population, with European, African and Amerindian ancestral roots is a model case for exploring the impact of population admixture on the frequency distribution of polymorphisms in pharmacogenes, and the design and interpretation of pharmacogenomics trials. Examples drawn from studies carried out by researchers of the Brazilian pharmacogenomics network, support the following conclusions: the distribution of polymorphisms varies across geographical regions and self-reported 'race/color' categories, and is best modeled as continuous functions of individual proportions of European and African ancestry; the differential frequency of polymorphisms impacts the calculations of sample sizes required for adequate statistical power in clinical trials performed in different segments of the Brazilian population; and extrapolation of pharmacogenomics data from well-defined ethnic groups to Brazilians is plagued with uncertainty...
February 2014: Pharmacogenomics
Matthew Oetjens, William S Bush, Kelly A Birdwell, Holli H Dilks, Erica A Bowton, Joshua C Denny, Russell A Wilke, Dan M Roden, Dana C Crawford
Calcineurin-inhibitors CI are immunosuppressive agents prescribed to patients after solid organ transplant to prevent rejection. Although these drugs have been transformative for allograft survival, long-term use is complicated by side effects including nephrotoxicity. Given the narrow therapeutic index of CI, therapeutic drug monitoring is used to prevent acute rejection from underdosing and acute toxicity from overdosing, but drug monitoring does not alleviate long-term side effects. Patients on calcineurin-inhibitors for long periods almost universally experience declines in renal function, and a subpopulation of transplant recipients ultimately develop chronic kidney disease that may progress to end stage renal disease attributable to calcineurin inhibitor toxicity (CNIT)...
2014: Pacific Symposium on Biocomputing
Kaname Nakatani
Personalized medicine based on pharmacogenomics is being developed at the clinical stage. Various evidence is accumulating in transplantation therapy. Tacrolimus, a calcineurin inhibitor, is usually used for immunosuppressive therapy after transplantation. Tacrolimus is mainly metabolized by cytochrome P450 isozymes, CYP3A4 and CYP3A5, expressed in the intestine as well as in the liver. Recent studies of pharmacogenomics have reported that several single nucleotide polymorphisms (SNPs) of CYP3A5 are correlated with gene expression and enzyme activity...
May 2013: Rinsho Byori. the Japanese Journal of Clinical Pathology
Brian Murray, Emily Hawes, Ruth-Ann Lee, Robert Watson, Mary W Roederer
Advances in the management of patients after solid organ transplantation have led to dramatic decreases in rates of acute rejection, but long-term graft and patient survival have remained unchanged. Individualized therapy after transplant will ideally provide adequate immunosuppression while limiting the adverse effects of drug therapy that significantly impact graft survival. Therapeutic drug monitoring represents the best approximation of individualized drug therapy in transplant at this time; however, obtaining pharmacogenomic data in transplant patients has the potential to enhance our current practice...
May 2013: Pharmacogenomics
Piotr K Janicki, Zakiyah Kadry
No abstract text is available yet for this article.
May 2013: Pharmacogenomics
S Manvizhi, B S Mathew, D H Fleming, G Basu, G T John
In patients undergoing renal transplantation, dose individualization for tacrolimus is routinely achieved with therapeutic drug monitoring (TDM). The patient started on 5.5 mg/day of tacrolimus had a significantly elevated tacrolimus trough concentration. The tacrolimus dose was regularly reduced following TDM at many time periods in the post transplant period but the tacrolimus concentration was consistently elevated. Genomic analysis done after four years revealed mutations in the genes encoding for CYP3A5 and MDR1 (2677G > T)...
January 2013: Indian Journal of Nephrology
Abdulkareem Albekairy, Abdulmalik Alkatheri, Shiro Fujita, Alan Hemming, Richard Howard, Alan Reed, Janet Karlix
BACKGROUND AND AIMS: Tacrolimus is a macrolide immunosuppressant used for prevention of allograft rejection in organ transplantation and metabolized in the liver and intestine by cytochrome P450 3A4 (CYP3A4) enzyme. A single nucleotide polymorphism (SNP) in the CYP3A4 promoter region has been identified. It has been shown that the presence of CYP3A4FNx011B allele (variant GG) is associated with a reduced catalytic activity of CYP3A4 in vivo. The aim of this study was to determine the role of CYP3A4FNx011B on tacrolimus dosing and clinical outcome in liver transplant recipients...
March 2013: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Katarzyna A Ellsworth, Irene Moon, Bruce W Eckloff, Brooke L Fridley, Gregory D Jenkins, Anthony Batzler, Joanna M Biernacka, Ryan Abo, Abra Brisbin, Yuan Ji, Scott Hebbring, Eric D Wieben, David A Mrazek, Richard M Weinshilboum, Liewei Wang
OBJECTIVES: FKBP51 (51 kDa immunophilin) acts as a modulator of the glucocorticoid receptor and a negative regulator of the Akt pathway. Genetic variation in FKBP5 plays a role in antidepressant response. The aim of this study was to comprehensively assess the role of genetic variation in FKBP5, identified by both Sanger and Next Generation DNA resequencing, as well as genome-wide single nucleotide polymorphisms (SNPs) associated with FKBP5 expression in the response to the selective serotonin reuptake inhibitor (SSRI) treatment of major depressive disorder...
March 2013: Pharmacogenetics and Genomics
Inés Llaudó, Helena Colom, Pepita Giménez-Bonafé, Joan Torras, Anna Caldés, Maria Sarrias, Josep M Cruzado, Federico Oppenheimer, Jaime Sánchez-Plumed, Miguel Ángel Gentil, Henrik Ekberg, Josep M Grinyó, Núria Lloberas
The function of the efflux pump P-glycoprotein (Pgp) and ABCB1 single nucleotide polymorphisms (SNPs) should be considered as important tools to deepen knowledge of drug nephrotoxicity and disposition mechanisms. The aim of this study is to investigate the association of C3435T, G2677T, C1236T, and T129C ABCB1 SNPs with Pgp activity and exposure to different immunosuppressive drugs in renal transplant patients. Patients included in the Symphony Pharmacogenomic substudy were genotyped for ABCB1 SNPs. According to the design, patients were randomized into four immunosuppressive regimens: low and standard dose of cyclosporine (n = 30), tacrolimus (n = 13), and sirolimus (n = 23) concomitantly with mycophenolate and steroids...
February 2013: Transplant International: Official Journal of the European Society for Organ Transplantation
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