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tacrolimus and polymorphism

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https://www.readbyqxmd.com/read/29775201/tacrolimus-population-pharmacokinetics-and-multiple-cyp3a5-genotypes-in-black-and-white-renal-transplant-recipients
#1
Olivia Campagne, Donald E Mager, Daniel Brazeau, Rocco C Venuto, Kathleen M Tornatore
Tacrolimus exhibits inter-patient pharmacokinetic variability attributed to CYP3A5 isoenzymes and the efflux transporter, P-glycoprotein. Most black renal transplant recipients require higher tacrolimus doses compared to whites to achieve similar troughs when race-adjusted recommendations are used. An established guideline provides tacrolimus genotype dosing recommendations based on CYP3A5*1(W/T) and loss of protein function variants: CYP3A5*3 (rs776746), CYP3A5*6 (rs10264272), CYP3A5*7 (rs41303343) and may provide more comprehensive race-adjusted dosing recommendations...
May 18, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29752633/clinical-pharmacokinetic-and-pharmacodynamic-considerations-in-the-treatment-of-ulcerative-colitis
#2
REVIEW
Sophie E Berends, Anne S Strik, Mark Löwenberg, Geert R D'Haens, Ron A A Mathôt
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on the severity, localization and history of IBD medication. According to the classic step-up approach, treatment with 5-aminosalicylic acid compounds is the first step in the treatment of mild to moderately active UC. Corticosteroids, such as prednisolone are used in UC patients with moderate to severe disease activity, but only for remission induction therapy because of side effects associated with long-term use...
May 12, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29733390/increase-in-tacrolimus-exposure-after-steroid-tapering-is-influenced-by-cyp3a5-and-pregnane-x-receptor-genetic-polymorphisms-in-renal-transplant-recipients
#3
Frank Stifft, Sander M J van Kuijk, Otto Bekers, Maarten H L Christiaans
Background: Tacrolimus, a drug for prevention of rejection after kidney transplantation, has a narrow therapeutic window and is metabolized by the cytochrome P540 3A (CYP3A) system. Tacrolimus exposure increases after steroid tapering in many patients. The pregnane X receptor (PXR)-a mediator for CYP3A-has a steroid receptor and might regulate CYP3A5 activity depending on single nucleotide polymorphisms (SNPs) of CYP3A5 or PXR. This may contribute to differences in tacrolimus exposure after steroid tapering...
May 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29731062/cyp3a5-3-genetic-polymorphism-and-tacrolimus-concentration-in-myanmar-renal-transplant-patients
#4
Y Y Htun, H K Swe, T M Saw
BACKGROUND: Genetic polymorphism is an important factor that influences tacrolimus concentrations and has the potential to predict the optimal dosage of tacrolimus in personalized medicine. Tacrolimus, a drug of narrow therapeutic index, is used in renal transplant recipients as an immunosuppressant agent. It is a substrate of cytochrome P450 3A (CYP3A) and has highly variable pharmacokinetic parameters. OBJECTIVE: The aim of this study was to identify the proportion of CYP3A5 gene polymorphism in Myanmar kidney transplant recipients and to determine the impact of CYP3A5 gene polymorphisms on tacrolimus level in CYP3A5 expressors and nonexpressors...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29708622/evaluation-of-tacrolimus-related-cyp3a5-genotyping-in-china-results-from-the-first-external-quality-assessment-exercise
#5
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/29691732/impact-of-the-cyp3a5-1-allele-on-the-pharmacokinetics-of-tacrolimus-in-japanese-heart-transplant-patients
#6
Takaya Uno, Kyoichi Wada, Sachi Matsuda, Yuka Terada, Akira Oita, Atsushi Kawase, Mitsutaka Takada
BACKGROUND AND OBJECTIVE: Tacrolimus, a major immunosuppressant used after transplantation, is associated with large interindividual variation involving genetic polymorphisms in metabolic processes. A common variant of the cytochrome P450 (CYP) 3A5 gene, CYP3A5*3, affects blood concentrations of tacrolimus. However, tacrolimus pharmacokinetics at the early stage of transplantation have not been adequately studied in heart transplantation. We retrospectively examined the impact of the CYP3A5 genotype on tacrolimus pharmacokinetics at the early stage of heart transplantation...
April 24, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29689130/a-donor-and-recipient-candidate-gene-association-study-of-allograft-loss-in-renal-transplant-recipients-receiving-a-tacrolimus-based-regimen
#7
Jean-Baptiste Woillard, Philippe Gatault, Nicolas Picard, Hélène Arnion, Dany Anglicheau, Pierre Marquet
This work investigated, in two large cohorts of French renal transplants treated with tacrolimus, the influence of donor and recipient ABCB1, CYP3A4 and CYP3A5 genotypes on the risk of allograft loss. A discovery and a replication population of 330 and 369 adult renal transplant patients, each from a different transplantation centre and all receiving a tacrolimus-based immunosuppressive regimen, were retrospectively genotyped. The influence of genetic factors and other known risk factors on allograft loss was investigated using multivariate Cox proportional hazard analyses...
April 24, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29665413/genetic-risk-factors-for-post-transplantation-diabetes-mellitus-in-chinese-han-renal-allograft-recipients-treated-with-tacrolimus
#8
Xiaoming Zhang, Tongyi Men, Haitao Liu, Xianduo Li, Jianning Wang, Jiaju Lv
BACKGROUND: Post-transplantation diabetes mellitus (PTDM) is a serious metabolic complication after kidney transplantation. The aim of this study was to explore the association of clinical variables and five selected single nucleotide polymorphisms (SNPs) with PTDM in Chinese Han renal allograft recipients taking tacrolimus (TAC). METHODS: A total of 129 non-diabetic, primary, Chinese Han renal allograft recipients treated with TAC were enrolled. Five SNPs (CYP3A5 rs776741, rs776746, rs15524, CYP24A1 rs2296241, and PPARG rs1801282) were genotyped and analyzed...
April 14, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29659047/the-changing-face-of-adult-posttransplant-lymphoproliferative-disorder-changes-in-histology-between-1999-2013
#9
Donald E Tsai, Stephen Bagley, Ran Reshef, Abraham Shaked, Roy D Bloom, Vivek Ahya, Lee Goldberg, Albert Chung, Fotini Debonera, Stephen J Schuster, Scott F Huntington
Posttransplant lymphoproliferative disorder (PTLD) typically presents with either polymorphic or monomorphic histology. While both are the end result of immunosuppressive therapies, their origins are felt to be different with different prognoses and responsiveness to therapy, resulting in two different malignancies. We attempted to confirm reports suggesting that the relative frequency of these two histologies is shifting over time. We analyzed 3040 adult PTLD cases in the UNOS OPTN database from 1999 to 2013...
April 16, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29621269/artificial-neural-network-model-for-predicting-the-bioavailability-of-tacrolimus-in-patients-with-renal-transplantation
#10
Kalluri Thishya, Kiran Kumar Vattam, Shaik Mohammad Naushad, Shree Bhushan Raju, Vijay Kumar Kutala
The objective of the current study was to explore the role of ABCB1 and CYP3A5 genetic polymorphisms in predicting the bioavailability of tacrolimus and the risk for post-transplant diabetes. Artificial neural network (ANN) and logistic regression (LR) models were used to predict the bioavailability of tacrolimus and risk for post-transplant diabetes, respectively. The five-fold cross-validation of ANN model showed good correlation with the experimental data of bioavailability (r2 = 0.93-0.96). Younger age, male gender, optimal body mass index were shown to exhibit lower bioavailability of tacrolimus...
2018: PloS One
https://www.readbyqxmd.com/read/29621122/survival-time-to-biopsy-proven-acute-rejection-and-tacrolimus-adverse-drug-reactions-in-pediatric-liver-transplantation
#11
Natalia Riva, Marcelo Dip, Esteban Halac, Paulo Cáceres Guido, Jean Baptiste Woillard, Nieves Licciardone, Debora Chan, Jefferson Buendía, Daniela Borgnia, Andrea Bosaleh, María Teresa de Davila, Oscar Imventarza, Paula Schaiquevich
BACKGROUND: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin-American cohort of pediatric liver transplant patients...
April 3, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29615122/effect-of-cyp3-a4-cyp3-a5-and-abcb1-gene-polymorphisms-on-the-clinical-efficacy-of-tacrolimus-in-the-treatment-of-nephrotic-syndrome
#12
Min Li, Min Xu, Wei Liu, Xin Gao
BACKGROUND: The efficacy of tacrolimus (TAC) is variable in the treatment of nephrotic syndrome (NS), which might be related to genetic variation among patients. Therefore, we aim to investigate the effects of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of TAC in the treatment of NS patients. Methods 100 NS patients were treated with TAC and prednisone and followed up for 3 months. Genotype differences (CYP3 A4*1G, CYP3 A5*3, ABCB1 1236C > T and ABCB1 2677G > T/A) were detected by Sanger sequencing...
April 3, 2018: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29611886/dose-optimisation-of-tacrolimus-with-therapeutic-drug-monitoring-and-cyp3a5-polymorphism-in-myasthenia-gravis-patients
#13
Di Chen, Shifang Hou, Ming Zhao, Xuelin Sun, Hua Zhang, Liping Yang
BACKGROUND AND PURPOSE: Tacrolimus was beneficial for treatment of myasthenia gravis (MG). And it has a narrow therapeutic range, therefore, therapeutic drug monitoring (TDM) is essential for tacrolimus to optimize dosage and prevent adverse reactions. However, no studies have explored the influencing factors of tacrolimus blood concentration in MG patients. Thus, we aimed to analyze the influencing factors and discuss how to optimal tacrolimus dosage for MG treatment. METHODS: The data of clinical characteristics, therapeutic drugs and adverse reactions of patients with MG who received tacrolimus were collected from 2013 to 2015 in Beijing Hospital...
April 3, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29603629/cyp3a5-3-and-abcb1-61a-g-significantly-influence-dose-adjusted-trough-blood-tacrolimus-concentrations-in-the-first-three-months-post-kidney-transplantation
#14
Rong Hu, Daniel T Barratt, Janet K Coller, Benedetta C Sallustio, Andrew A Somogyi
Tacrolimus (TAC) is a first-line immunosuppressant used to prevent organ rejection after kidney transplantation. There is large inter-individual variability in its pharmacokinetics. Single nucleotide polymorphisms (SNPs) in genes encoding TAC metabolising enzymes cytochromes P450 3A4/5 (CYP3A4/5), P-glycoprotein efflux transporter (ABCB1), their expression regulator pregnane X receptor (NR1I2), and CYP3A co-factor cytochrome P450 reductase (POR), have been studied for their effects on tacrolimus disposition...
March 30, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29563827/cyp3a5-polymorphisms-in-renal-transplant-recipients-influence-on-tacrolimus-treatment
#15
REVIEW
Lucy Chen, G V Ramesh Prasad
Tacrolimus is a commonly used immunosuppressant after kidney transplantation. It has a narrow therapeutic range and demonstrates wide interindividual variability in pharmacokinetics, leading to potential underimmunosuppression or toxicity. Genetic polymorphism in CYP3A5 enzyme expression contributes to differences in tacrolimus bioavailability between individuals. Individuals carrying one or more copies of the wild-type allele *1 express CYP3A5, which increases tacrolimus clearance. CYP3A5 expressers require 1...
2018: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29550576/influence-of-cyp3a5-genetic-differences-in-tacrolimus-on-quantitative-interstitial-fibrosis-and-long-term-graft-function-in-kidney-transplant-recipients
#16
Naoki Komine, Shigeru Satoh, Mitsuru Saito, Kazuyuki Numakura, Takamitsu Inoue, Hiroshi Tsuruta, Shintaro Narita, Atsushi Komatsuda, Hiroshi Nanjo, Hideaki Kagaya, Takenori Niioka, Masatomo Miura, Yoko Mitobe, Tomonori Habuchi
The impact of CYP3A5 polymorphisms on clinical outcomes is controversial. The present study investigated the impact of CYP3A5 genetic differences on the development of interstitial fibrosis (IF) from 0 h to 1 year post-transplantation in biopsy sections from 96 living kidney recipients under the same target trough regimen of tacrolimus. The relationships between CYP3A5 polymorphisms and long-term graft function and death-censored graft survival were also examined. A quantitative analysis of IF was performed using computer-assisted imaging on virtual slides...
March 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29546446/cyp3a4-and-gck-genetic-polymorphisms-are-the-risk-factors-of-tacrolimus-induced-new-onset-diabetes-after-transplantation-in-renal-transplant-recipients
#17
Daohua Shi, Tiancheng Xie, Jie Deng, Peiguang Niu, Weizhen Wu
PURPOSE: We intend to investigate the association between tacrolimus-induced new-onset diabetes after transplantation (NODAT) and polymorphisms of CYP3A4, CYP3A5, ATP-binding cassette transporter sub-family C member 8 (ABCC8), and glucokinase (GCK) in renal transplant recipients. METHODS: Polymorphisms of CYP3A4 *18B, CYP3A5 *3, ABCC8 T-3C, and GCK G-30A were genotyped in 169 renal transplant recipients. Trough concentrations of tacrolimus were detected by an ELISA kit...
March 15, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29535109/off-label-use-of-tacrolimus-in-children-with-henoch-sch%C3%A3-nlein-purpura-nephritis-a-pilot-study
#18
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/29454235/donor-and-recipient-p450-gene-polymorphisms-influence-individual-pharmacological-effects-of-tacrolimus-in-chinese-liver-transplantation-patients
#19
Jianyu Liu, Yabo Ouyang, Dexi Chen, Bo Yao, Dongdong Lin, Zhiqiang Li, Yunjin Zang, Huan Liu, Xiaoyue Fu
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants...
April 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29393157/tacrolimus-dose-optimization-strategy-for-refractory-ulcerative-colitis-based-on-the-cytochrome-p450-3a5-polymorphism-prediction-using-trough-concentration-after-24-hours
#20
Motoyuki Onodera, Katsuya Endo, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Yoichi Kakuta, Kenichi Negoro, Yoshitaka Kinouchi, Tooru Shimosegawa
BACKGROUND: In the tacrolimus treatment for refractory ulcerative colitis (UC), dose adjustment is necessary because the required doses to keep appropriate drug concentrations are significantly different among individuals. Cytochrome P450 (CYP) 3A5 polymorphism affects tacrolimus blood concentrations. However, it is difficult to obtain genetic information in real clinical practice. In the present study, we investigated possible factors that may predict CYP3A5 polymorphism and proposed a dose optimization strategy based on the obtained predicting factors...
2018: Digestion
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