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tacrolimus and polymorphism

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https://www.readbyqxmd.com/read/28224698/determinants-of-the-magnitude-of-interaction-between-tacrolimus-and-voriconazole-posaconazole-in-solid-organ-recipients
#1
Thomas Vanhove, Hanneke Bouwsma, Luuk Hilbrands, Jesse J Swen, Isabel Spriet, Pieter Annaert, Bart Vanaudenaerde, Geert Verleden, Robin Vos, Dirk 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
#2
Beuy Joob, Viroj Wiwanitkit
No abstract text is available yet for this article.
2017: J Nephropharmacol
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
#3
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
#4
Markus Riegersperger, Max Plischke, Corinna Steinhauser, Anita Jallitsch-Halper, Guerkan Sengoelge, Wolfgang C Winkelmayer, Gere Sunder-Plassmann, Manuela F Ouml Dinger
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
#5
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
#6
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...
January 23, 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
#7
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
#8
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/27885697/dynamic-effects-of-cyp3a5-polymorphism-on-dose-requirement-and-trough-concentration-of-tacrolimus-in-renal-transplant-recipients
#9
P Chen, J Li, J Li, R Deng, Q Fu, J Chen, M Huang, X Chen, C Wang
WHAT IS KNOWN AND OBJECTIVE: Tacrolimus is a widely used immunosuppressive drug with marked pharmacokinetic variability partly due to CYP3A5 polymorphism. Our study aimed to investigate the dynamic effects of CYP3A5 genotypes on dose requirement and trough concentration (C0 ) of tacrolimus in renal transplant recipients. METHODS: A total of 194 Chinese renal transplant recipients received oral tacrolimus twice daily. Whole-blood C0 of tacrolimus were measured on the 3rd day, 7th day, 14th day, 1st month, 3rd month and 6th month post-transplantation...
February 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27747372/foxp3-rs3761548-polymorphism-is-associated-with-tacrolimus-induced-acute-nephrotoxicity-in-renal-transplant-patients
#10
Zhuo Wu, Qinxia Xu, Xiaoyan Qiu, Zheng Jiao, Ming Zhang, Mingkang Zhong
PURPOSE: The purpose of this study was to investigate the potential impact of FOXP3 and CCDC22 gene polymorphisms on efficacy and safety of tacrolimus (TAC) in renal transplant patients. METHODS: Genetic polymorphisms were detected in 114 Chinese renal transplant patients who were on TAC-based maintenance immunosuppression and were followed up for at least 2 years. The relationships between FOXP3 rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22 rs2294021 polymorphisms and clinical outcomes such as acute rejection, TAC-induced acute nephrotoxicity, and pneumonia were investigated by using Kaplan-Meier estimates and multivariate Cox regression analysis...
January 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27717793/the-effect-of-cyp3a5-genetic-polymorphisms-on-adverse-events-in-patients-with-ulcerative-colitis-treated-with-tacrolimus
#11
Ayumi Asada, Shigeki Bamba, Yukihiro Morita, Kenichiro Takahashi, Hirotsugu Imaeda, Atsushi Nishida, Osamu Inatomi, Mitsushige Sugimoto, Masaya Sasaki, Akira Andoh
BACKGROUND: Tacrolimus is an immunosuppressive agent, used in the remission induction therapy of ulcerative colitis (UC). AIMS: We investigated the correlation between CYP3A5 genetic polymorphisms and the adverse events in patients with UC. The pharmacokinetics of tacrolimus after oral administration were also analyzed. METHODS: We enrolled 29 hospitalized patients with UC received oral tacrolimus. Genotyping for CYP3A5 A6986G (rs776746) was performed using Custom TaqMan(®) SNP genotyping assays...
January 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27706725/effect-of-pregnane-x-receptor-polymorphisms-on-tacrolimus-blood-concentrations-and-the-resulting-adverse-reactions-in-kidney-transplantation-recipients
#12
Z P Wang, M Zhao, Q S Qu, S Z Miao
We investigated the effect of pregnane X receptor (PXR) polymorphisms on tacrolimus (FK506) blood trough concentrations and the associated adverse reactions in kidney transplantation recipients (KTRs). Polymerase chain reaction (PCR)-restriction fragment length polymorphism was used to detect the genotypes of single nucleotide polymorphism loci in 336 KTRs. The PXR six-base deletion mutation was classified using specific allele PCR, and the FK506 blood trough concentration in the KTRs was measured by chemiluminescent microparticle immunoassay...
September 16, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27597269/predictive-modeling-of-tacrolimus-dose-requirement-based-on-high-throughput-genetic-screening
#13
C Damon, M Luck, L Toullec, I Etienne, M Buchler, B Hurault de Ligny, G Choukroun, A Thierry, C Vigneau, B Moulin, A-E Heng, J-F Subra, C Legendre, A Monnot, A Yartseva, M Bateson, P Laurent-Puig, D Anglicheau, P Beaune, M A Loriot, E Thervet, N Pallet
Any biochemical reaction underlying drug metabolism depends on individual gene-drug interactions and on groups of genes interacting together. Based on a high-throughput genetic approach, we sought to identify a set of covariant single-nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C0 ) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable-selection strategy to reinforce the stability of the variable-selection process and multivariate modeling...
September 6, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27569929/impact-of-foxp3-polymorphisms-on-the-blood-level-of-tacrolimus-in-renal-transplant-recipients
#14
J Ge, J Wang, H Zhao, K Li, Y Jing, G Li
INTRODUCTION: Tacrolimus is an immunosuppressive medication for organ transplantation. FOXP3(+) T regulatory cells (Tregs) play roles in suppression of rejection and induction of graft tolerance. This study aimed to evaluate the correlation between the polymorphism of FOXP3 and the blood level of tacrolimus in renal transplant recipients. METHODS: This retrospective study included 100 renal transplant recipients receiving tacrolimus treatment and 100 healthy control subjects...
July 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27536671/lupus-nephritis-a-different-disease-in-european-patients
#15
REVIEW
Vladimir Tesar, Zdenka Hruskova
BACKGROUND: Lupus nephritis (LN) is still associated with significant mortality and substantial risk of progression to end-stage renal failure. Its outcome is related to the class and severity of LN and response to treatment, and it is poorer in patients with renal relapses. Ethnicity has a relatively well-defined impact on the outcome of the patients and their response to treatment and must always be taken into consideration in treatment decisions. SUMMARY: In this article, we provide a review of the impact of ethnicity on the prevalence of systemic lupus erythematosus (SLE), the proportion of patients with SLE developing LN, outcomes of SLE and LN and response of LN to treatment...
September 2015: Kidney Diseases
https://www.readbyqxmd.com/read/27536670/lupus-nephritis-in-asia-clinical-features-and-management
#16
REVIEW
Desmond Y H Yap, Tak Mao Chan
BACKGROUND: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. SUMMARY: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed...
September 2015: Kidney Diseases
https://www.readbyqxmd.com/read/27511886/associations-of-the-cyp3a5-3-and-cyp3a4-1g-polymorphisms-with-the-pharmacokinetics-of-oral-midazolam-and-the-urinary-6%C3%AE-hydroxycortisol-cortisol-ratio-as-markers-of-cyp3a-activity-in-healthy-male-chinese
#17
S W Chan, Y Xiao, M Hu, O Q P Yin, T T W Chu, B S P Fok, V H L Lee, B Tomlinson
WHAT IS KNOWN AND OBJECTIVE: The oral plasma clearance of midazolam and the ratio of 6β-hydroxycortisol (6β-OHF) to cortisol (F) in urine are two potential markers for evaluating CYP3A activity in vivo. We assessed the influence of two common CYP3A polymorphisms on the pharmacokinetics of oral midazolam and urinary ratio of 6β-OHF/F in healthy Chinese. METHODS: Single oral 15 mg doses of midazolam were given to 20 healthy male Chinese subjects who were genotyped for the CYP3A5*3 and CYP3A4*1G polymorphisms...
October 2016: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27503662/pharmacokinetics-of-a-once-daily-dose-of-tacrolimus-early-after-liver-transplantation-with-special-reference-to-cyp3a5-and-abcb1-single-nucleotide-polymorphisms
#18
Yoichi Miyata, Nobuhisa Akamatsu, Yasuhiko Sugawara, Junichi Kaneko, Takehito Yamamoto, Hiroshi Suzuki, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Sumihito Tamura, Norihiro Kokudo
BACKGROUND The aim of the present study was to investigate the pharmacokinetics of the once-daily tacrolimus formulation (QD form) in relation to polymorphisms of the donor cytochrome P450 family 3 sub-family A polypeptide 5 (CYP3A5) gene and recipient adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1) gene. MATERIAL AND METHODS A total of 80 consecutive living-donor liver transplant (LDLT) recipients were started on the QD form of tacrolimus (day 1), and 60 patients were completely followed for 7 days early after liver transplantation in order to evaluate the pharmacokinetics...
August 9, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27501475/comparative-performance-of-oral-midazolam-clearance-and-plasma-4%C3%AE-hydroxycholesterol-to-explain-interindividual-variability-in-tacrolimus-clearance
#19
Thomas Vanhove, Hylke de Jonge, Henriëtte de Loor, Pieter Annaert, Ulf Diczfalusy, Dirk R J Kuypers
AIMS: We compared the CYP3A4 metrics weight-corrected midazolam apparent oral clearance (MDZ Cl/F/W) and plasma 4β-hydroxycholesterol/cholesterol (4β-OHC/C) as they relate to tacrolimus (TAC) Cl/F/W in renal transplant recipients. METHODS: For a cohort of 147 patients, 8 h area under the curve (AUC) values for TAC and oral MDZ were calculated besides measurement of 4β-OHC/C. A subgroup of 70 patients additionally underwent intravenous erythromycin breath test (EBT) and were administered the intravenous MDZ probe...
December 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27486667/significant-association-between-toll-like-receptor-gene-polymorphisms-and-posttransplantation-diabetes-mellitus
#20
Jin Sug Kim, Seul Ki Kim, Ji Yoon Park, Yang Gyun Kim, Joo Young Moon, Sang Ho Lee, Chun Gyoo Ihm, Tae Won Lee, Su Kang Kim, Joo-Ho Chung, Sun Woo Kang, Tae Hee Kim, Yeong Hoon Kim, Kyung Hwan Jeong
BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is an important metabolic complication after renal transplantation. Activation of the innate immune system via toll-like receptors (TLRs) is implicated in the pathogenesis of insulin resistance and deficiency. Although links between diabetes, dysregulated innate immune responses, and the TLR signaling pathway have been reported, no study so far has investigated their associations with PTDM. In this study, we ascertained whether single nucleotide polymorphisms (SNPs) in TLRs are associated with PTDM in the Korea population...
2016: Nephron
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