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tacrolimus and polymorphism

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https://www.readbyqxmd.com/read/28624888/steady-state-pharmacokinetics-of-mycophenolic-acid-in-renal-transplant-patients-exploratory-analysis-of-the-effects-of-cyclosporine-recipients-and-donors-abcc2-gene-variants-and-their-interactions
#1
N Božina, Z Lalić, S Nađ-Škegro, A Borić-Bilušić, T Božina, Ž Kaštelan, V Trkulja
PURPOSE: The study aims to evaluate the impact of recipients' and donors' polymorphisms in multidrug resistance-associated protein 2 (MRP2) gene ABCC2 -24C>T and 1249G>A on disposition of mycophenolic acid (MPA) and their interaction with cyclosporine (CsA) (compared to tacrolimus, TAC) in stable de novo adult renal transplant patients of Croatian origin. METHODS: A total of 68 recipient-donor pairs were genotyped. Steady-state pharmacokinetics of MPA was assessed by the model-independent method...
June 18, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28593920/influence-of-cyp3a4-and-cyp3a5-polymorphisms-on-tacrolimus-and-sirolimus-exposure-in-stable-kidney-transplant-recipients
#2
Erika Y Tamashiro, Claudia R Felipe, Fabiana D V Genvigir, Alice C Rodrigues, Antony B Campos, Rosario D C Hirata, Helio Tedesco-Silva, Jose O Medina-Pestana
BACKGROUND: Polymorphisms in genes encoding for drug-metabolizing enzymes and drug transporters are among multiple factors that modulate the pharmacokinetic variability of tacrolimus (TAC) and sirolimus (SRL). This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) on TAC and SRL dose-adjusted concentrations (C0/D) in stable kidney transplant recipients. METHODS: This is an exploratory and prospective study, which includes 46 stable kidney transplant recipients...
May 24, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28590937/tacrolimus-dose-requirement-based-on-the-cyp3a5-genotype-in-renal-transplant-patients
#3
Lihui Qu, Yingying Lu, Meike Ying, Bingjue Li, Chunhua Weng, Zhoutao Xie, Ludan Liang, Chuan Lin, Xian Yang, Shi Feng, Yucheng Wang, Xiujin Shen, Qin Zhou, Ying Chen, Zhimin Chen, Jianyong Wu, Weiqiang Lin, Yi Shen, Jing Qin, Hang Xu, Feng Xu, Junwen Wang, Jianghua Chen, Hong Jiang, Hongfeng Huang
Tacrolimus (FK506) and cyclosporine A (CsA) are widely used to protect graft function after renal transplantation. The aim of the present study is to determine whether the single nucleotide polymorphism of CYP3A5 is a predictive index of FK506 dose requirement, and also the selection yardstick of FK506 or CsA treatment.We tested archival peripheral blood of 218 kidney recipients for CYP3A5 genotyping with PCR-SSP. Meanwhile, the dose of FK506 and CsA was recorded, blood concentration of the drugs was measured, and graft outcome was monitored...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28540692/effects-of-cyp3a5-polymorphisms-on-tacrolimus-pharmacokinetics-in-pediatric-kidney-transplantation-a-systematic-review-and-meta-analysis-of-observational-studies
#4
Yi-Ping Zong, Zi-Jie Wang, Wan-Li Zhou, Wei-Min Zhou, Tie-Liang Ma, Zheng-Kai Huang, Chun-Chun Zhao, Zhen Xu, Ruo-Yun Tan, Min Gu
BACKGROUND: CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs. METHODS: A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials...
May 24, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28437851/fexofenadine-a-putative-in-vivo-p-glycoprotein-probe-fails-to-predict-clearance-of-the-substrate-tacrolimus-in-renal-recipients
#5
Thomas Vanhove, Thomas Bouillon, Henriëtte de Loor, Pieter Annaert, Dirk R J Kuypers
Whether combined use of probe drugs for CYP3A4 and P-glycoprotein can clarify the relative contribution of these proteins to pharmacokinetic variability of a dual substrate like tacrolimus has never been assessed. Seventy renal recipients underwent simultaneous 8-hour pharmacokinetic profiles for tacrolimus, the CYP3A4 probe midazolam and the putative P-glycoprotein probe fexofenadine. Patients were genotyped for polymorphisms in CYP3A5, CYP3A4, ABCB1, ABCC2 and SLCO2B1, -1B1 and 1B3. Carriers of the ABCB1 2677G>A polymorphism displayed lower fexofenadine Cmax (-66%; P=0...
April 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28435308/association-of-the-ppp3ca-c-249g-a-variant-with-clinical-outcomes-of-tacrolimus-based-therapy-in-kidney-transplant-recipients
#6
Patricia C Salgado, Fabiana Dv Genvigir, Claudia R Felipe, Helio Tedesco-Silva, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario Dc Hirata
BACKGROUND: The effects of genetic variants related to the pharmacodynamic mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety have been poorly explored. This study was performed to investigate the influence of the PPP3CA c.249G>A variant on the clinical outcomes of kidney transplant recipients. PATIENTS AND METHODS: A total of 148 Brazilian patients received tacrolimus (TAC)-based immunosuppressive therapy for 90 days post-kidney transplantation...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28401703/tacrolimus-population-pharmacokinetics-according-to-cyp3a5-genotype-and-clinical-factors-in-chinese-adult-kidney-transplant-recipients
#7
REVIEW
H J Zhang, D Y Li, H J Zhu, Y Fang, T S Liu
WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is characterized by a narrow therapeutic index and a considerable inter- and intraindividual pharmacokinetic variability. The aim of our study was to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant of Chinese patients, identify factors especially CYP3A5*3 genetic polymorphism that explain variability, and determine dosage regimens. METHODS: Pharmacogenomic data obtained from 83 Chinese kidney transplant patients treated with tacrolimus were determined using polymerase chain reaction-restriction fragment length polymorphism analysis...
April 11, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28340819/influence-of-proton-pump-inhibitors-on-mycophenolic-acid-pharmacokinetics-in-patients-with-renal-transplantation-and-the-relationship-with-cytochrome-2c19-gene-polymorphism
#8
H S Ciftci, M S Karadeniz, T Tefik, Y Caliskan, H Yazıcı, E Demir, A Turkmen, I Nane, F S Oguz, F Aydin
BACKGROUND: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28320277/mechanisms-of-brain-glucocorticoid-resistance-in-stress-induced-psychopathologies
#9
REVIEW
V M Merkulov, T I Merkulova, N P Bondar
Exposure to stress activates the hypothalamic-pituitary-adrenal axis and leads to increased levels of glucocorticoid (GC) hormones. Prolonged elevation of GC levels causes neuronal dysfunction, decreases the density of synapses, and impairs neuronal plasticity. Decreased sensitivity to glucocorticoids (glucocorticoid resistance) that develops as a result of chronic stress is one of the characteristic features of stress-induced psychopathologies. In this article, we reviewed the published data on proposed molecular mechanisms that contribute to the development of glucocorticoid resistance in brain, including changes in the expression of the glucocorticoid receptor (GR) gene, biosynthesis of GR isoforms, and GR posttranslational modifications...
March 2017: Biochemistry. Biokhimii︠a︡
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
#10
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...
March 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28271256/impact-of-the-cyp3a5-genotype-on-the-distributions-of-dose-adjusted-trough-concentrations-and-incidence-of-rejection-in-japanese-renal-transplant-recipients-receiving-different-tacrolimus-formulations
#11
Takenori Niioka, Hideaki Kagaya, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Ryohei Yamamoto, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
BACKGROUND: We investigated the impact of the CYP3A5 genotype on the distributions of dose-adjusted trough concentrations (C 0h/D) and the incidence of rejection in Japanese recipients taking twice-daily (Tac-BID, n = 140) or modified-release once-daily (Tac-QD, n = 80) tacrolimus formulations for 1 year after renal transplantation. METHODS: Logistic regression analysis was carried out to estimate the distinction rate of CYP3A5 genotypes based on the C 0h/D of Tac-BID or Tac-QD...
March 7, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28246425/influence-of-il-18-and-il-10-polymorphisms-on-tacrolimus-elimination-in-chinese-lung-transplant-patients
#12
Xiaoqing Zhang, Jiandong Xu, Junwei Fan, Tao Zhang, Yuping Li, Boxiong Xie, Wei Zhang, Shengtao Lin, Ling Ye, Yuan Liu, Gening Jiang
Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped...
2017: Disease Markers
https://www.readbyqxmd.com/read/28224698/determinants-of-the-magnitude-of-interaction-between-tacrolimus-and-voriconazole-posaconazole-in-solid-organ-recipients
#13
T Vanhove, H Bouwsma, L Hilbrands, J J Swen, I Spriet, P Annaert, B Vanaudenaerde, G Verleden, R Vos, D R J Kuypers
Administration of azole antifungals to tacrolimus-treated solid organ recipients results in a major drug-drug interaction characterized by increased exposure to tacrolimus. The magnitude of this interaction is highly variable but cannot currently be predicted. We performed a retrospective analysis of 126 solid organ recipients (95 lung, 31 kidney) co-treated with tacrolimus and voriconazole (n = 100) or posaconazole (n = 26). Predictors of the change in tacrolimus dose-corrected trough concentrations (C/D) between baseline and tacrolimus-azole co-therapy were assessed using linear mixed modeling...
February 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28197525/hsd11b1-rs846908-polymorphisms-and-tacrolimus-concentrations-quantum-chemical-analysis-and-implication-in-patients-with-renal-transplantation
#14
Beuy Joob, Viroj Wiwanitkit
No abstract text is available yet for this article.
2017: Journal of Nephropharmacology
https://www.readbyqxmd.com/read/28195062/the-influence-of-the-tumor-necrosis-factor-alpa-308g-a-polymorphism-on-the-efficacy-of-immunosuppressive-therapy-in-patients-after-kidney-transplantation
#15
M M Kotowski, A Bogacz, J Bartkowiak-Wieczorek, J Sienko, D Procyk, K Dziewanowski, M Ostrowski, B Czerny, E Grzeskowiak, B Machalinski
Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28164520/the-effect-of-abcb1-polymorphisms-on-serial-tacrolimus-concentrations-in-stable-austrian-long-term-kidney-transplant-recipients
#16
Markus Riegersperger, Max Plischke, Corinna Steinhauser, Anita Jallitsch-Halper, Guerkan Sengoelge, Wolfgang C Winkelmayer, Gere Sunder-Plassmann, Manuela Födinger
BACKGROUND: The multidrug resistance 1 gene (ABCB1) encodes P-glycoprotein (PGP), mainly expressed in the liver and engaged in metabolism of drugs including the immunosuppressant tacrolimus (TAC). ABCB1 single nucleotide polymorphisms (SNP) may significantly alter pharmacokinetics and influence TAC concentrations of kidney transplant recipients (KTR). METHODS: The genotype distribution of ABCB1 1236C>T, 2677G>T/A and 3435C>T was investigated among 96 Austrian KTR who were converted from cyclosporin to TAC...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28135009/atp-binding-cassette-subfamily-b-member-1-1236c-t-polymorphism-significantly-affects-the-therapeutic-outcome-of-tacrolimus-in-patients-with-refractory-ulcerative-colitis
#17
Motoyuki Onodera, Katsuya Endo, Yoichi Kakuta, Masatake Kuroha, Tomoya Kimura, Keiichiro Hiramoto, Yoshitake Kanazawa, Kenichi Negoro, Hisashi Shiga, Yoshitaka Kinouchi, Tooru Shimosegawa
BACKGROUND AND AIM: Tacrolimus is now considered to be one of the main therapeutic options for refractory ulcerative colitis. Both cytochrome P-450 3A5 (CYP3A5) and ATP-binding cassette subfamily B member 1 (ABCB1) associated with tacrolimus metabolism are known to have several genetic polymorphisms. However, it remains controversial whether these polymorphisms affect the therapeutic efficacy for ulcerative colitis. We aimed to investigate the influence of both CYP3A5 and ABCB1 polymorphisms on the efficacy of tacrolimus in ulcerative colitis treatment under the tight dose-adjusting strategy...
January 30, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28112181/il-3-and-ctla4-gene-polymorphisms-may-influence-the-tacrolimus-dose-requirement-in-chinese-kidney-transplant-recipients
#18
Mou-Ze Liu, Hai-Yan He, Yue-Li Zhang, Yong-Fang Hu, Fa-Zhong He, Jian-Quan Luo, Zhi-Ying Luo, Xiao-Ping Chen, Zhao-Qian Liu, Hong-Hao Zhou, Ming-Jie Shao, Ying-Zi Ming, Hua-Wen Xin, Wei Zhang
The highly variable pharmacokinetics and narrow therapeutic window of tacrolimus (TAC) has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms (SNPs) with TAC dose-adjusted concentrations (C0/D) was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients...
March 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28050888/a-new-cyp3a5-3-and-cyp3a4-22-cluster-influencing-tacrolimus-target-concentrations-a-population-approach
#19
Franc Andreu, Helena Colom, Laure Elens, Teun van Gelder, Ronald H N van Schaik, Dennis A Hesselink, Oriol Bestard, Joan Torras, Josep M Cruzado, Josep M Grinyó, Nuria Lloberas
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the CYP3A5 and CYP3A4 genes have been reported to be an important cause of variability in the pharmacokinetics of tacrolimus in renal transplant patients. The aim of this study was to merge all of the new genetic information available with tacrolimus pharmacokinetics to generate a more robust population model with data from renal transplant recipients. METHODS: Tacrolimus exposure data from 304 renal transplant recipients were collected throughout the first year after transplantation and were simultaneously analyzed with a population pharmacokinetic approach using NONMEM(®) version 7...
January 3, 2017: Clinical Pharmacokinetics
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
#20
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
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