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tacrolimus pharmacogenetic

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https://www.readbyqxmd.com/read/29708622/evaluation-of-tacrolimus-related-cyp3a5-genotyping-in-china-results-from-the-first-external-quality-assessment-exercise
#1
Guigao Lin, Xiao Zhang, Kuo Zhang, Yanxi Han, Liming Tan, Jinming Li
BACKGROUND: Tacrolimus is the most widely used immunosuppressant in solid organ transplant patients. The cytochrome P450 3A5 (CYP3A5) has been proved to be associated with tacrolimus dose requirement. Molecular detection for CYP3A5 genotyping is demanded for the optimization of treatments of tacrolimus. METHODS: To achieve the consistency and accuracy of the testing results, the Chinese National Center for Clinical Laboratories (NCCL) organized a national external quality assessment(EQA) program to evaluate the performance of laboratories providing CYP3A5 genotyping...
April 30, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29701126/-what-do-we-know-about-tacrolimus-pharmacogenetics-in-transplant-recipients
#2
Dirk Rj Kuypers
No abstract text is available yet for this article.
April 27, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29629825/cyp3a-pharmacogenetic-association-with-tacrolimus-pharmacokinetics-differs-based-on-route-of-drug-administration
#3
Amy L Pasternak, Lu Zhang, Daniel L Hertz
Tacrolimus is prescribed to the majority of transplant recipients to prevent graft rejection, and although patients are maintained on oral administration, nonoral routes of administration are frequently used in the initial post-transplant period. CYP3A5 genotype is an established predictor of oral tacrolimus dose requirements, and clinical guideline recommendations exist for CYP3A5-guided dose selection. However, the association between CYP3A5 and nonoral tacrolimus administration is currently poorly understood, and differs from the oral tacrolimus relationship...
April 9, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29550633/current-progress-of-tacrolimus-dosing-in-solid-organ-transplant-recipients-pharmacogenetic-considerations
#4
REVIEW
Xiao Zhang, Guigao Lin, Liming Tan, Jinming Li
Tacrolimus is effective for the prevention of acute rejection, but is also highly toxic and has great intra- and inter-individual variability in transplant patients. Genetic variation and other factors influence the response of an individual to tacrolimus treatment. Therefore, even if therapeutic drug monitoring is universally applied, rejection and toxicity still occur. Although the appropriate action on pharmacogenomic variability provides a cornerstone for the precise tacrolimus prescription, at present there are many obstacles to translating it into clinical practice...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29535109/off-label-use-of-tacrolimus-in-children-with-henoch-sch%C3%A3-nlein-purpura-nephritis-a-pilot-study
#5
Dong-Feng Zhang, Guo-Xiang Hao, Chun-Zhen Li, Yan-Jun Yang, Fu-Juan Liu, Ling Liu, Xiao-Ying Yuan, Rui-Hong Li, Lei Dong, Qian Dong, Evelyne Jacqz-Aigrain, Wei Zhao
BACKGROUND: Tacrolimus is used off-label in the treatment of Henoch-Schönlein purpura nephritis (HSPN) in children, with limited evidence-based data. Based on clinical empirical experience and mechanism of action, tacrolimus might be promoted as treatment for childhood HSPN. The objectives of this pilot study were to assess its effectiveness and safety, and to explore the potential impact of CYP3A5 genotype. METHODS: Children with HSPN receiving tacrolimus as empirical treatment were included in this prospective, observational study...
March 13, 2018: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/29479631/clinical-aspects-of-tacrolimus-use-in-paediatric-renal-transplant-recipients
#6
Agnieszka Prytuła, Teun van Gelder
The calcineurin inhibitor tacrolimus, cornerstone of most immunosuppressive regimens, is a drug with a narrow therapeutic window: underexposure can lead to allograft rejection and overexposure can result in an increased incidence of infections, toxicity and malignancies. Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. This review focusses on the clinical aspects of tacrolimus pharmacodynamics, such as efficacy and toxicity. Factors affecting tacrolimus pharmacokinetics, including pharmacogenetics and the rationale for routine CYP3A5*1/*3 genotyping in prospective paediatric renal transplant recipients, are also reviewed...
February 26, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29399716/pharmacogenetics-of-post-transplant-diabetes-mellitus-in-children-with-renal-transplantation-treated-with-tacrolimus
#7
Pauline Lancia, Tiphaine Adam de Beaumais, Valéry Elie, Florentine Garaix, Marc Fila, François Nobili, Bruno Ranchin, Pascale Testevuide, Tim Ulinski, Wei Zhao, Georges Deschênes, Evelyne Jacqz-Aigrain
BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a major complication of immunosuppressive therapy, with many risk factors reported in adults with renal transplantation. The objective of this study was to investigate potential non-genetic and genetic risk factors of PTDM in children with renal transplantation treated with tacrolimus. METHODS: A national database was screened for patients developing PTDM within 4 years following tacrolimus introduction. PTDM was defined as glucose disorder requiring anti-diabetic treatment...
February 4, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29380698/pharmacokinetics-pharmacodynamics-and-pharmacogenetics-of-tacrolimus-in-kidney-transplantation
#8
Meng Yu, Mouze Liu, Wei Zhang, Yingzi Ming
Tacrolimus(Tac) is a first-line immunosuppressive drug used mainly after allogeneic organ transplant to reduce rejection. Tac is proved to be effective in preventing acute rejection, yet it has considerable toxicity and displays marked inter-individual variability in its pharmacokinetics(PK) and pharmacodynamics(PD). Established pharmacogenetics(PG) discoveries are being investigated on drug absorption, metabolism, disposition, excretion and response for better clinical application. The purpose of the present review is to picture the current status of Tac PG, and discuss the relationship between its PK and PD in kidney transplantation...
January 29, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29229354/comparative-clinical-trial-of-the-variability-factors-of-the-exposure-indices-used-for-the-drug-monitoring-of-two-tacrolimus-formulations-in-kidney-transplant-recipients
#9
Pierre Marquet, Laetitia Albano, Jean-Baptiste Woillard, Lionel Rostaing, Nassim Kamar, Charlotte Sakarovitch, Philippe Gatault, Matthias Buchler, Bernard Charpentier, Eric Thervet, Elisabeth Cassuto
BACKGROUND: Several studies found differences in tacrolimus whole blood trough levels (C0) or area-under-the curve (AUC) between the twice-daily (Tac-BID) and once-daily (Tac-OD) formulations given to kidney transplant recipients at equal doses. As C0 is widely used as a surrogate of the AUC for individual dose adjustment, this study investigated the correlation and proportionality between C0 and the 24h-AUC, depending on the formulation, time post-transplantation, pharmacogenetics traits and other individual characteristics...
March 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29199543/genetic-variations-of-the-xenoreceptors-nr1i2-and-nr1i3-and-their-effect-on-drug-disposition-and-response-variability
#10
Litaty Céphanoée Mbatchi, Jean-Paul Brouillet, Alexandre Evrard
NR1I2 (PXR) and NR1I3 (CAR) are nuclear receptors that are classified as xenoreceptors. Upon activation by various xenobiotics, including marketed drugs, they regulate the transcription level of major drug-metabolizing enzymes and transporters and facilitate the elimination of xenobiotics from the body. The modulation of the activity of these two xenoreceptors by various ligands is a major source of pharmacokinetic variability of environmental origin. NR1I2 and NR1I3 genetic polymorphisms can affect the pharmacokinetics and therapeutic response to many drugs, such as irinotecan, tacrolimus and atazanavir...
January 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29162334/results-of-asertaa-a-randomized-prospective-crossover-pharmacogenetic-study-of-immediate-release-versus-extended-release-tacrolimus-in-african-american-kidney-transplant-recipients
#11
Jennifer Trofe-Clark, Daniel C Brennan, Patricia West-Thielke, Michael C Milone, Mary Ann Lim, Robin Neubauer, Vincenza Nigro, Roy D Bloom
BACKGROUND: Differences in tacrolimus dosing across ancestries is partly attributable to polymorphisms in CYP3A5 genes that encode tacrolimus-metabolizing cytochrome P450 3A5 enzymes. The CYP3A5*1 allele, preponderant in African Americans, is associated with rapid metabolism, subtherapeutic concentrations, and higher dose requirements for tacrolimus, all contributing to worse outcomes. Little is known about the relationship between CYP3A5 genotype and the tacrolimus pharmacokinetic area under the curve (AUC) profile in African Americans or whether pharmacogenetic differences exist between conventional twice-daily, rapidly absorbed, immediate-release tacrolimus (IR-Tac) and once-daily extended-release tacrolimus (LifeCycle Pharma Tac [LCPT]) with a delayed absorption profile...
March 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28342282/pharmacokinetic-and-pharmacogenetic-analysis-of-immunosuppressive-agents-after-laparoscopic-sleeve-gastrectomy
#12
RANDOMIZED CONTROLLED TRIAL
Tayyab S Diwan, Alicia B Lichvar, Abbie D Leino, Alexander A Vinks, Uwe Christians, Adele R Shields, Michael A Cardi, Tsuyoshi Fukuda, Tomoyuki Mizuno, Tiffany Kaiser, E Steve Woodle, Rita R Alloway
BACKGROUND: Severe obesity has been shown to limit access to renal transplantation in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics. METHODS: This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study...
June 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28316087/influence-of-abcc2-cyp2c8-and-cyp2j2-polymorphisms-on-tacrolimus-and-mycophenolate-sodium-based-treatment-in-brazilian-kidney-transplant-recipients
#13
Fabiana D V Genvigir, Alvaro M Nishikawa, Claudia R Felipe, Helio Tedesco-Silva, Nagilla Oliveira, Antony B C Salazar, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario D C Hirata
STUDY OBJECTIVE: To investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and dose-adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients. DESIGN: Pharmacogenetic analysis of patients enrolled in a previously published study...
May 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28229376/the-pharmacogenetics-of-tacrolimus-in-corticosteroid-sparse-pediatric-and-adult-kidney-transplant-recipients
#14
Mads Juul Madsen, Troels K Bergmann, Kim Brøsen, Helle Charlotte Thiesson
INTRODUCTION: Tacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Studies have shown an association between the CYP3A5 genotype and tacrolimus dose-adjusted trough concentrations. Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism. Furthermore, pharmacokinetic interaction between corticosteroid treatment and tacrolimus has been shown...
June 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28176850/application-of-machine-learning-models-to-predict-tacrolimus-stable-dose-in-renal-transplant-recipients
#15
Jie Tang, Rong Liu, Yue-Li Zhang, Mou-Ze Liu, Yong-Fang Hu, Ming-Jie Shao, Li-Jun Zhu, Hua-Wen Xin, Gui-Wen Feng, Wen-Jun Shang, Xiang-Guang Meng, Li-Rong Zhang, Ying-Zi Ming, Wei Zhang
Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the "derivation cohort" to develop dose-prediction algorithm, while the remaining 20% constituted the "validation cohort" to test the final selected algorithm...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28030534/single-nucleotide-polymorphism-of-cyp3a5-impacts-the-exposure-to-tacrolimus-in-pediatric-renal-transplant-recipients-a-pharmacogenetic-substudy-of-the-twist-trial
#16
RANDOMIZED CONTROLLED TRIAL
Heiko Billing, Britta Höcker, Alexander Fichtner, Rita van Damme-Lombaerts, Styrbjorn Friman, Jenö Jaray, Karel Vondrak, Eniko Sarvary, Luca Dello Strologo, Michael Oellerich, Nicolas von Ahsen, Burkhard Tönshoff
BACKGROUND: The pharmacokinetics of tacrolimus (TAC) and mycophenolic acid (MPA) are highly variable. An impact of single-nucleotide polymorphisms (SNPs) of the genes coding for enzymes and transporters involved in the pharmacokinetics of TAC and/or MPA is intuitively conceivable. Accordingly, we sought to analyze the influence of different SNPs on TAC and MPA exposure in pediatric renal transplant recipients. METHODS: A subpopulation of 37 patients (median age: 12...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27966227/tacrolimus-dose-requirements-in-paediatric-renal-allograft-recipients-are-characterized-by-a-biphasic-course-determined-by-age-and-bone-maturation
#17
Noël Knops, Jean Herman, Maria van Dyck, Yasaman Ramazani, Edward Debbaut, Rita van Damme-Lombaerts, Elena Levtchenko, Lambertus P van den Heuvel, Steffen Fieuws, Dirk Kuypers
AIMS: Despite longstanding recognition of significant age-dependent differences in drug disposition during childhood, the exact course and the underlying mechanisms are not known. Our aim was to determine the course and determinants of individual relative dose requirements, during long-term follow-up in children on tacrolimus. METHODS: This was a cohort study in a tertiary hospital with standardized annual pharmacokinetic (PK) follow-up (AUC0-12hr ) in recipients of a renal allograft (≤19 years), between 1998 and 2015...
April 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27591328/con-the-use-of-calcineurin-inhibitors-in-the-treatment-of-lupus-nephritis
#18
Maria Fernandez Nieto, David R Jayne
Lupus nephritis (LN) therapy has limited efficacy due to its toxicity, and LN patients suffer high risks of renal and cardiovascular morbidity and mortality. Calcineurin inhibitors (CNIs) have been used for over >30 years in LN treatment and are an established alternative therapy for Class V nephritis, but uncertainty remains about their role in proliferative disease or in the maintenance of remission. More recently, the combination of CNIs with mycophenolate mofetil (MMF) and glucocorticoid combination therapy, 'multitarget' therapy and the use of tacrolimus as opposed to ciclosporin has received attention...
October 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27417340/therapeutic-monitoring-of-the-immuno-modulating-drugs-in-systemic-lupus-erythematosus
#19
REVIEW
Chi Chiu Mok
Despite the emergence of newer immunomodulating agents for systemic lupus erythematosus (SLE), a substantial proportion of patients still do not respond optimally. While the mechanisms for the differential responses to drug therapy are unclear, variation in drug exposure with the same dosing protocol related to pharmacogenetic and pharmacokinetic factors may contribute. This article discusses the use of therapeutic drug monitoring (TDM) to optimize therapies in SLE patients. Areas covered: Evidence on the relationship between blood levels and efficacy/toxicity of immuno-modulating drugs such as hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) and the calcineurin inhibitors that are often used in SLE...
January 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27314545/cyp3a-pharmacogenetics-and-tacrolimus-disposition-in-adult-heart-transplant-recipients
#20
Kimberly M Deininger, Anh Vu, Robert L Page, Amrut V Ambardekar, JoAnn Lindenfeld, Christina L Aquilante
BACKGROUND: Cytochrome P450 (CYP) 3A polymorphisms are associated with variable CYP3A metabolizing enzyme activity and tacrolimus pharmacokinetics. We sought to determine the singular and combined impact of CYP3A4*22 and CYP3A5*3 variants on tacrolimus drug disposition in adult heart transplant recipients. METHODS: The retrospective study included 76 patients greater than one year post-heart transplant and receiving tacrolimus. Patients were genotyped for CYP3A4*22 and CYP3A5*3, and combined genotypes were classified as follows: extensive metabolizers (EM, CYP3A4*1/*1+CYP3A5*1 carriers), intermediate metabolizers (IM, CYP3A4*1/*1+CYP3A5*3/*3, or CYP3A4*22 carriers+CYP3A5*1 carriers), and poor metabolizers (PM, CYP3A4*22 carriers+CYP3A5*3/*3)...
September 2016: Clinical Transplantation
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