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Tacrolimus pharmacokinetics

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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/29766530/population-pharmacokinetics-of-tacrolimus-in-paediatric-systemic-lupus-erythematosus-based-on-real-world-study
#2
D-D Wang, J-M Lu, Q Li, Z-P Li
WHAT IS KNOWN AND OBJECTIVES: Different population pharmacokinetics (PPK) models of tacrolimus have been established in various populations. However, the tacrolimus PPK model in paediatric systemic lupus erythematosus (PSLE) is still undefined. This study aimed to establish the tacrolimus PPK model in Chinese PSLE. METHODS: A total of nineteen Chinese patients with PSLE from real-world study were characterized with nonlinear mixed-effects modelling (NONMEM). The impact of demographic features, biological characteristics, and concomitant medications was evaluated...
May 15, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29753157/treosulfan-fludarabine-and-low-dose-total-body-irradiation-for-children-and-young-adults-with-acute-myeloid-leukemia-or-myelodysplastic-syndrome-undergoing-allogeneic-hematopoietic-cell-transplantation-a-prospective-phase-ii-trial-of-the-pediatric-blood-and
#3
Eneida R Nemecek, Ralf A Hilger, Alexia Adams, Bronwen E Shaw, Deidre Kiefer, Jennifer Le-Rademacher, John E Levine, Gregory Yanik, Wing Leung, Julie-An Talano, Paul Haut, David Delgado, Neena Kapoor, Aleksandra Petrovic, Roberta Adams, Rabi Hanna, Hemalatha Rangarajan, Jignesh Dalal, Joseph Chewning, Michael R Verneris, Stacy Epstein, Lauri Burroughs, Evelio D Perez-Albuerne, Michael A Pulsipher, Colleen Delaney
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (1-19) underwent allogeneic HCT for AML in first (n=18), second (n=11), third or greater remission (n=3); or MDS (n=8) using bone marrow (n=25), peripheral blood stem cells (n=5) or cord blood (n=9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2 /day (BSA ≤ 0...
May 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29752633/clinical-pharmacokinetic-and-pharmacodynamic-considerations-in-the-treatment-of-ulcerative-colitis
#4
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/29750317/mycophenolate-mofetil-for-sustained-remission-in-nephrotic-syndrome
#5
Uwe Querfeld, Lutz T Weber
The clinical application of mycophenolate mofetil (MMF) has significantly widened beyond the prophylaxis of acute and chronic rejections in solid organ transplantation. MMF has been recognized as an excellent treatment option in many immunologic glomerulopathies. For children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) experiencing steroid toxicity, MMF has been recommended as a steroid-sparing drug. Uncontrolled studies in patients with FRNS and SDSN have shown that many patients can achieve sustained remission of proteinuria with MMF monotherapy...
May 11, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29746396/development-of-an-abbreviatted-mycophenolic-acid-area-under-the-time-concentration-curve-for-renal-transplanted-patients-under-enteric-coated-mycophenolate-sodium-a-comparison-with-critical-analysis-of-available-equations
#6
Elias David-Neto, Ana Heloisa Triboni, Fernanda Ramos, Fabiana Agena, Paschoalina Romano
BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS) is frequently used in renal transplantation. The pharmacokinetic profile of mycophenolic acid (MPA) shows a broad range of time-to-maximum-concentration (Tmax) that limits the use of a single MPA concentration to calculate the area under the time-concentration curve (AUC). For both research and clinical MPA monitoring, measuring a complete AUC is troublesome to the center and patients. METHODS: We obtained 171 complete MPA-AUC12h (0, 20,40,60,90,120, 180, 240, 360, 480, 600, 720 min) from 59 adult (54±16 years) patients (29 male, 43 whites) who have been receiving stable doses of Tacrolimus/EC-MPS and steroids...
May 4, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29735215/limited-sampling-strategy-for-estimating-mycophenolic-acid-exposure-on-day-7-post-transplant-for-two-mycophenolate-mofetil-formulations-derived-from-20-chinese-renal-transplant-recipients
#7
W Cai, Q Cai, N Xiong, Y Qin, L Lai, X Sun, Y Hu
PURPOSE: To assess the pharmacokinetic properties of mycophenolate mofetil (MMF) dispersible tablets and capsules by the enzyme multiplied immunoassay technique (EMIT) in Chinese kidney transplant recipients in the early post-transplantation phase and to develop the equations to predict mycophenolic acid (MPA) area under the 12-hour concentration-time curve (AUC0-12h ) using a limited sampling strategy (LSS). METHODS: Forty patients who underwent renal transplantation from brain-dead donors were randomly divided into dispersible tablets (Sai KE Ping; Hangzhou Zhongmei Huadong Pharma) and capsules (Cellcept; Roche Pharma, Why, NSW, Australia) groups, and treated with MMF combined with combination tacrolimus and prednisone as a basic immunosuppressive regimen...
May 4, 2018: Transplantation Proceedings
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
#8
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
#9
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/29703388/update-of-green-tea-interactions-with-cardiovascular-drugs-and-putative-mechanisms
#10
REVIEW
José Pablo Werba, Shingen Misaka, Monica Gianna Giroli, Kenju Shimomura, Manuela Amato, Niccolò Simonelli, Lorenzo Vigo, Elena Tremoli
Many patients treated with cardiovascular (CV) drugs drink green tea (GT), either as a cultural tradition or persuaded of its putative beneficial effects for health. Yet, GT may affect the pharmacokinetics and pharmacodynamics of CV compounds. Novel GT-CV drug interactions were reported for rosuvastatin, sildenafil and tacrolimus. Putative mechanisms involve inhibitory effects of GT catechins at the intestinal level on influx transporters OATP1A2 or OATP2B1 for rosuvastatin, on CYP3A for sildenafil and on both CYP3A and the efflux transporter p-glycoprotein for tacrolimus...
April 2018: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/29691732/impact-of-the-cyp3a5-1-allele-on-the-pharmacokinetics-of-tacrolimus-in-japanese-heart-transplant-patients
#11
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/29667720/mycophenolate-mofetil-administered-every-8-hours-in-combination-with-tacrolimus-is-efficacious-in-the-prophylaxis-of-acute-graft-versus-host-disease-in-childhood-adolescent-and-young-adult-allogeneic-stem-cell-transplantation-recipients
#12
Olga Militano, Mehmet F Ozkaynak, Brinda Mehta, Carmella van deVen, Carl Hamby, Mitchell S Cairo
BACKGROUND: The optimal dose and schedule of mycophenolate mofetil (MMF) in pediatric allogeneic stem cell transplant recipients remains to be determined. We previously reported safety and pharmacokinetics of MMF at 900 mg/m2 q6h dosing. This study was conducted to investigate the efficacy of tacrolimus plus q8h MMF dosing for acute graft versus host disease (GVHD) prophylaxis in a heterogeneous population of children, adolescent, young adult allogeneic stem cell transplant recipients, utilizing multiple allogeneic donor sources...
April 18, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29665413/genetic-risk-factors-for-post-transplantation-diabetes-mellitus-in-chinese-han-renal-allograft-recipients-treated-with-tacrolimus
#13
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/29648533/the-effect-of-fluconazole-on-the-pharmacokinetics-of-everolimus-and-tacrolimus-in-a-heart-transplant-recipient-a-case-report
#14
Kazuki Nakagita, Kyoichi Wada, Yuka Terada, Sachi Matsuda, Nobue Terakawa, Akira Oita, Mitsutaka Takada
OBJECTIVE: Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been used in combination with calcineurin inhibitors (tacrolimus and cyclosporine) to prevent allograft rejection following organ transplantation. In heart transplant recipients, everolimus should be maintained at a target blood concentration of 3 - 8 ng/mL, in combination with reduced-dose calcineurin inhibitors and therefore, requires strict monitoring. Fluconazole, an azole antifungal agent, affects blood concentration of tacrolimus by inhibiting the cytochromes P450 (CYP) 3A4 and 3A5...
April 12, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29629825/cyp3a-pharmacogenetic-association-with-tacrolimus-pharmacokinetics-differs-based-on-route-of-drug-administration
#15
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/29603629/cyp3a5-3-and-abcb1-61a-g-significantly-influence-dose-adjusted-trough-blood-tacrolimus-concentrations-in-the-first-three-months-post-kidney-transplantation
#16
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/29578937/determination-of-tacrolimus-concentration-and-protein-expression-of-p-glycoprotein-in-single-human-renal-core-biopsies
#17
Veronica Krogstad, Nils Tore Vethe, Ida Robertsen, Grete Hasvold, Anne-Marthe Due Ose, Monica Hermann, Anders Mikal Andersen, Joe Chan, Morten Skauby, My Hanna Sofia Svensson, Anders Åsberg, Hege Christensen
BACKGROUND: Tacrolimus is currently the cornerstone of immunosuppressive protocols for renal transplant recipients. Despite therapeutic whole blood monitoring, tacrolimus is associated with nephrotoxicity and it has been hypothesized that intrarenal accumulation of tacrolimus and/or its metabolites are involved. As tacrolimus is a substrate of P-glycoprotein (P-gp), the expression and activity of this efflux transporter could influence the levels of tacrolimus in renal tissue. The primary aim of this study was to develop and validate a method for quantification of tacrolimus in tissue homogenates from single human renal core biopsies...
March 23, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29569341/bariatric-surgery-in-solid-organ-transplant-patients-long-term-follow-up-results-of-outcome-safety-and-effect-on-immunosuppression
#18
Renana Yemini, Eviatar Nesher, Janos Winkler, Idan Carmeli, Carmil Azran, Matan Ben David, Eytan Mor, Andrei Keidar
The surgical risk of transplanted patients is high, and the modified gastrointestinal anatomy after BS may lead to pharmacokinetic alterations in the absorption of immunosuppressive drugs. Data on outcomes of bariatric surgery (BS) and the safety and feasibility of maintaining immunosuppression and graft safety among solid-organ transplanted patients are scarce. In the current study, weight loss, improvement in comorbidities and changes in dosage and trough levels of immunosuppression drugs before and after BS were analyzed for all transplanted patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in our institution between 11/2011-1/2017...
March 22, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29563827/cyp3a5-polymorphisms-in-renal-transplant-recipients-influence-on-tacrolimus-treatment
#19
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/29550633/current-progress-of-tacrolimus-dosing-in-solid-organ-transplant-recipients-pharmacogenetic-considerations
#20
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...
March 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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