Summary: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.

Top Publications

  1. ncbi Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern?
    A D Ormerod
    Br J Dermatol 153:701-5. 2005
  2. ncbi One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients
    H T Silva
    Hospital do Rim E Hipertansã, Sao Paulo, Brazil
    Am J Transplant 7:595-608. 2007
  3. ncbi Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus
    Roy D Bloom
    Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Am Soc Nephrol 13:1374-80. 2002
  4. ncbi Reduced exposure to calcineurin inhibitors in renal transplantation
    Henrik Ekberg
    Lund University, Malmo, Sweden
    N Engl J Med 357:2562-75. 2007
  5. pmc Calcineurin is essential for survival during membrane stress in Candida albicans
    M Cristina Cruz
    Department of Genetics, Duke University Medical Center, Durham, NC 27710, USA
    EMBO J 21:546-59. 2002
  6. ncbi Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study
    B K Krämer
    V Medizinische Klinik, Universitatsklinikum Mannheim, University of Heidelberg, Mannheim, Germany
    Am J Transplant 10:2632-43. 2010
  7. ncbi The ORION study: comparison of two sirolimus-based regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients
    S M Flechner
    Cleveland Clinic Foundation, OH, USA
    Am J Transplant 11:1633-44. 2011
  8. ncbi Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen
    A M Shapiro
    Surgical Medical Research Institute and the Department of Surgery, University of Alberta, Edmonton, Canada
    N Engl J Med 343:230-8. 2000
  9. ncbi The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units
    K Wu
    Kosan Biosciences Inc, Hayward, CA 94545, USA
    Gene 251:81-90. 2000
  10. ncbi Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation
    Christine E Staatz
    School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia
    Clin Pharmacokinet 43:623-53. 2004

Detail Information

Publications352 found, 100 shown here

  1. ncbi Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern?
    A D Ormerod
    Br J Dermatol 153:701-5. 2005
  2. ncbi One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients
    H T Silva
    Hospital do Rim E Hipertansã, Sao Paulo, Brazil
    Am J Transplant 7:595-608. 2007
    Once-daily tacrolimus extended-release formulation (Prograf XL, formerly referred to as MR or MR4) was compared with the twice-a-day tacrolimus formulation (TAC) and cyclosporine microemulsion (CsA), all administered in combination with ..
  3. ncbi Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus
    Roy D Bloom
    Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Am Soc Nephrol 13:1374-80. 2002
    ..none have been clearly identified as predisposing to the increased PTDM frequency observed in patients on tacrolimus. Hepatitis C virus (HCV) has been associated with diabetes and is a significant renal transplant comorbidity...
  4. ncbi Reduced exposure to calcineurin inhibitors in renal transplantation
    Henrik Ekberg
    Lund University, Malmo, Sweden
    N Engl J Med 357:2562-75. 2007
    ..Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens...
  5. pmc Calcineurin is essential for survival during membrane stress in Candida albicans
    M Cristina Cruz
    Department of Genetics, Duke University Medical Center, Durham, NC 27710, USA
    EMBO J 21:546-59. 2002
    ..albicans mutants, against other Candida species, or when combined with different azoles. We propose that calcineurin is part of a membrane stress survival pathway that could be targeted for therapy...
  6. ncbi Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study
    B K Krämer
    V Medizinische Klinik, Universitatsklinikum Mannheim, University of Heidelberg, Mannheim, Germany
    Am J Transplant 10:2632-43. 2010
    ..1:1-randomized, parallel-group, noninferiority study compared the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) and once-daily tacrolimus prolonged release (Tacrolimus QD; Advagraf), combined with ..
  7. ncbi The ORION study: comparison of two sirolimus-based regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients
    S M Flechner
    Cleveland Clinic Foundation, OH, USA
    Am J Transplant 11:1633-44. 2011
    Safety and efficacy of two sirolimus (SRL)-based regimens were compared with tacrolimus (TAC) and mycophenolate mofetil (MMF)...
  8. ncbi Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen
    A M Shapiro
    Surgical Medical Research Institute and the Department of Surgery, University of Alberta, Edmonton, Canada
    N Engl J Med 343:230-8. 2000
    ..Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year...
  9. ncbi The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units
    K Wu
    Kosan Biosciences Inc, Hayward, CA 94545, USA
    Gene 251:81-90. 2000
    ..Gene 169, 1-7), consistent with labeling data showing that rapamycin biosynthesis uses only malonyl and methylmalonyl extender units...
  10. ncbi Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation
    Christine E Staatz
    School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia
    Clin Pharmacokinet 43:623-53. 2004
    ..review is to analyse critically the recent literature on the clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplant recipients...
  11. ncbi Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis
    Kanako Kitahara
    Department of Immunology, Toho University School of Medicine, Japan
    Curr Opin Rheumatol 19:238-45. 2007
    The calcineurin inhibitors cyclosporine and tacrolimus are important treatments for patients with active rheumatoid arthritis, especially in cases of resistance or intolerance to methotrexate or other disease-modifying antirheumatic drugs...
  12. pmc Association of MDR1 gene SNPs and haplotypes with the tacrolimus dose requirements in Han Chinese liver transplant recipients
    Xiaobo Yu
    Key Lab of Combined Multi Organ Transplantation, The First Affiliated Hospital, School of Medicine, Zhejiang University, Ministry of Public Health, Hangzhou, Zhejiang, China
    PLoS ONE 6:e25933. 2011
    This work seeks to evaluate the association between the C/D ratios (plasma concentration of tacrolimus divided by daily dose of tacrolimus per body weight) of tacrolimus and the haplotypes of MDR1 gene combined by C1236T (rs1128503), ..
  13. pmc Improvement of FK506 production in Streptomyces tsukubaensis by genetic enhancement of the supply of unusual polyketide extender units via utilization of two distinct site-specific recombination systems
    Dandan Chen
    Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China
    Appl Environ Microbiol 78:5093-103. 2012
  14. ncbi Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis
    Eleonora Patsenker
    Institute of Clinical Pharmacology and Visceral Research, University of Bern, Switzerland
    J Hepatol 55:388-98. 2011
    ..The aim of the present study was to compare the potential of the commonly used immunosuppressants to halt experimental liver fibrosis progression...
  15. pmc Novel polymorphisms associated with tacrolimus trough concentrations: results from a multicenter kidney transplant consortium
    Pamala A Jacobson
    Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
    Transplantation 91:300-8. 2011
    The CYP4503A5*1 genotype is associated with lower tacrolimus concentrations...
  16. ncbi Lower variability of tacrolimus trough concentration after conversion from prograf to advagraf in stable kidney transplant recipients
    Ming Ju Wu
    Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
    Transplantation 92:648-52. 2011
    ..Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation...
  17. pmc Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate
    Jennifer N Andexer
    Biotica, Chesterford Research Park, Cambridge CB10 1XL, United Kingdom
    Proc Natl Acad Sci U S A 108:4776-81. 2011
    ..Also, purified Hyg5 catalyzed the predicted conversion of chorismate into 3-hydroxybenzoate. FkbO, RapK, Hyg5, and Bra8 are thus founder members of a previously unrecognized family of enzymes acting on chorismate...
  18. ncbi Tacrolimus for myasthenia gravis: a clinical study of 212 patients
    José M Ponseti
    Unit of Myasthenia Gravis, Department of Surgery, Hospital General Universitari Vall d Hebron, Passeig Vall d Hebron 119 129, E 08035 Barcelona, Spain
    Ann N Y Acad Sci 1132:254-63. 2008
    b>Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia gravis (MG) patients to affect muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing muscular strength), ..
  19. ncbi Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference
    Pierre Wallemacq
    Department of Clinical Chemistry, Laboratory of Toxicology and Therapeutic Drug Monitoring, Universite Catholique de Louvain, University Hospital St Luc, 10 Hippocrate Avenue, Brussels, Belgium
    Ther Drug Monit 31:139-52. 2009
    In 2007, a consortium of European experts on tacrolimus (TAC) met to discuss the most recent advances in the drug/dose optimization of TAC taking into account specific clinical situations and the analytical methods currently available and ..
  20. ncbi Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction
    Daniel C Brennan
    Washington University School of Medicine, Department of Internal Medicine, St Louis, Missouri, USA
    Am J Transplant 5:582-94. 2005
    Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon ..
  21. ncbi FKBP family proteins: immunophilins with versatile biological functions
    Cong Bao Kang
    School of Biological Science, Nanyang Technological University, Singapore, Singapore
    Neurosignals 16:318-25. 2008
    ..This review focuses on molecular characteristics of the canonical and noncanonical FKBP family members and the biological functions of their ligands in performing neuroprotective and neurotrophic activities...
  22. doi Effect on kidney graft survival of reducing or discontinuing maintenance immunosuppression after the first year posttransplant
    Gerhard Opelz
    Transplantation 86:371-6. 2008
    ..Data are scarce concerning the impact of maintenance immunosuppression dose reductions posttransplant...
  23. pmc Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS-1E beta-cells
    L A Øzbay
    Department of Nephrology, Aarhus University Hospital, Skejby, Aarhus, Denmark
    Br J Pharmacol 162:136-46. 2011
    Introducing the calcineurin inhibitors cyclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) decrease survival rates.
  24. ncbi Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II
    Christine E Staatz
    University of Queensland, Brisbane, Australia
    Clin Pharmacokinet 49:207-21. 2010
    The calcineurin inhibitors ciclosporin (cyclosporine) and tacrolimus are immunosuppressant drugs used for the prevention of organ rejection following transplantation...
  25. ncbi Calcineurin phosphatase activity and immunosuppression. A review on the role of calcineurin phosphatase activity and the immunosuppressive effect of cyclosporin A and tacrolimus
    K A Jørgensen
    Research Laboratory, Department of Renal Medicine C, Skejby Sygehus, Arhus University Hospital, Arhus N, Denmark
    Scand J Immunol 57:93-8. 2003
    The mode of immunosuppressive action of tacrolimus (FK506) and cyclosporin A has been elucidated...
  26. ncbi Absence of influence of concomitant administration of rabeprazole on the pharmacokinetics of tacrolimus in adult living-donor liver transplant patients: a case-control study
    Keiko Hosohata
    Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan
    Drug Metab Pharmacokinet 24:458-63. 2009
    This study assesses the effects of rabeprazole on the pharmacokinetics of tacrolimus, considering the cytochrome P450 (CYP) 2C19 and CYP3A5 genotypes of living-donor liver transplant patients (native intestine) and their corresponding ..
  27. pmc Changes of antimicrobial peptides and transepidermal water loss after topical application of tacrolimus and ceramide-dominant emollient in patients with atopic dermatitis
    Kui Young Park
    Department of Dermatology, Chung Ang University College of Medicine, Seoul, Korea
    J Korean Med Sci 25:766-71. 2010
    ..b>Tacrolimus and ceramide-dominant emollients are effective in the treatment of AD by preventing the production of ..
  28. ncbi A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients
    Bernard Charpentier
    Service de Nephrologie, Hopital de Bicetre, Le Kremlin Bicetre, France
    Transplantation 75:844-51. 2003
    ..A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney ..
  29. ncbi Once daily tacrolimus formulation: monitoring of plasma levels, graft function, and cardiovascular risk factors
    A Meçule
    DAI Nefro Urologico, Specialità Chirurgiche e Trapianti d Organo Paride Stefanini, Roma, Italy
    Transplant Proc 42:1317-9. 2010
    Advagraf, an extended release formulation of tacrolimus, is administered once daily during the morning fast...
  30. ncbi Reduced C0 concentrations and increased dose requirements in renal allograft recipients converted to the novel once-daily tacrolimus formulation
    Hylke de Jonge
    Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
    Transplantation 90:523-9. 2010
    Recently, a once-daily prolonged release formulation of tacrolimus (TacOD) has been approved for the prevention of renal allograft rejection...
  31. ncbi Increased adherence after switch from twice daily calcineurin inhibitor based treatment to once daily modified released tacrolimus in heart transplantation: a pre-experimental study
    A O Doesch
    Department of Cardiology, University of Heidelberg, Heidelberg, Germany
    Transplant Proc 42:4238-42. 2010
    Modified release tacrolimus (TAC) is a new, once-daily oral formulation of the established immunosuppressive agent TAC. Simplification of regimen has been associated with better adherence...
  32. ncbi Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation
    Qisi Wu
    The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China
    Eur Neurol 64:169-77. 2010
    b>Tacrolimus (TAC) is an immunosuppressant drug discovered in 1984 by Fujisawa Pharmaceutical Co., Ltd...
  33. ncbi Tacrolimus versus cyclosporine as primary immunosuppression after heart transplantation: systematic review with meta-analyses and trial sequential analyses of randomised trials
    Luit Penninga
    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato Biliary Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
    Eur J Clin Pharmacol 66:1177-87. 2010
    We conducted a systematic review of randomized trials to compare the benefits and harms of tacrolimus versus cyclosporine as primary immunosuppression after heart transplantation.
  34. ncbi Kidney function after islet transplant alone in type 1 diabetes: impact of immunosuppressive therapy on progression of diabetic nephropathy
    Paola Maffi
    Department of Medicine, Transplant Unit, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy
    Diabetes Care 30:1150-5. 2007
    ..The aim of our study was to assess the impact of the Edmonton immunosuppressive protocol (tacrolimus-sirolimus association) on kidney function.
  35. ncbi Novel double coated nanocapsules for intestinal delivery and enhanced oral bioavailability of tacrolimus, a P-gp substrate drug
    Taher Nassar
    Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, P O Box 12065, Jerusalem, 91120, Israel
    J Control Release 133:77-84. 2009
    ..of double coated nanocapsules to improve the oral bioavailability of a P-glycoprotein (P-gp) substrate drug, tacrolimus, without modulating the physiological activity of the P-gp pump...
  36. pmc Regulation by FK506 and rapamycin of Ca2+ release from the sarcoplasmic reticulum in vascular smooth muscle: the role of FK506 binding proteins and mTOR
    D MacMillan
    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
    Br J Pharmacol 158:1112-20. 2009
  37. ncbi Once- versus twice-daily tacrolimus: are the formulations truly equivalent?
    Katherine A Barraclough
    Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Brisbane, QLD, Australia
    Drugs 71:1561-77. 2011
    b>Tacrolimus is a cornerstone immunosuppressant agent in the prevention of organ rejection following transplantation...
  38. ncbi Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors' dose requirements and trough blood levels in stable renal transplant patients
    Laure Elens
    Department of Clinical Chemistry, Erasmus University Medical Center, Gravendijkwal 230, Rotterdam, The Netherlands
    Pharmacogenomics 12:1383-96. 2011
    CYP3A4 is involved in the oxidative metabolism of many drugs and xenobiotics including the immunosuppressants tacrolimus (Tac) and cyclosporine (CsA)...
  39. ncbi Coronary endothelial vasomotor function and vascular remodeling in heart transplant recipients randomized for tacrolimus or cyclosporine immunosuppression
    Paraskevi Petrakopoulou
    Medizinische Klinik und Poliklinik I, Ludwig Maximilians University of Munich, Munich, Germany
    J Am Coll Cardiol 47:1622-9. 2006
    This study aimed to compare changes in coronary endothelial function, systemic endothelin-1 (ET-1) levels, and vascular remodeling in heart transplant recipients randomized to cyclosporin A (CyA) or tacrolimus (Tac) immunosuppression.
  40. ncbi The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia
    Ashenafi Y Tilahun
    Department of Immunology, Mayo Clinic, Rochester, MN 55906, USA
    Microbes Infect 14:528-36. 2012
    ..Given the biological functions of SAg, we evaluated the efficacy of tacrolimus, a potent immunosuppressive agent, in the prophylaxis and therapy of staphylococcal TSS and pneumonia using ..
  41. ncbi In vitro effects of cyclosporine A and tacrolimus on regulatory T-cell proliferation and function
    Céline Miroux
    CNRS UMR8161, Institut de Biologie de Lille, Universités Lille Nord de France, Lille, France
    Transplantation 94:123-31. 2012
    ..Regulatory T cells (Tregs) may be beneficial in tolerance but deleterious in recurrent hepatitis C. We evaluated the effects of cyclosporine or tacrolimus, the principal immunosuppressive drugs, on Treg proliferation and function.
  42. ncbi In vivo CYP3A4 activity, CYP3A5 genotype, and hematocrit predict tacrolimus dose requirements and clearance in renal transplant patients
    H de Jonge
    Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
    Clin Pharmacol Ther 92:366-75. 2012
    b>Tacrolimus is metabolized by CYP3A4 and CYP3A5 and is characterized by a narrow therapeutic index and highly variable pharmacokinetics...
  43. ncbi Once-daily extended-release versus twice-daily standard-release tacrolimus in kidney transplant recipients: a systematic review
    Elaine T L Ho
    Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia 2145
    Transplantation 95:1120-8. 2013
    ..We aimed to identify, appraise, and synthesize the current evidence comparing the relative safety and efficacy of the recently introduced daily versus standard twice-daily tacrolimus administration.
  44. ncbi Tacrolimus induces glomerular injury via endothelial dysfunction caused by reactive oxygen species and inflammatory change
    Kengo Kidokoro
    Department of Nephrology and Hypertension, Kawasaki Medical School Kurashiki, Okayama, Japan
    Kidney Blood Press Res 35:549-57. 2012
    The immunosuppressive drug tacrolimus (FK506) is used clinically to reduce the rejection rate in patients with kidney transplantation; however, the resultant nephrotoxicity remains a serious problem...
  45. ncbi Effect of tacrolimus on myocardial infarction is associated with inflammation, ROS, MAP kinase and Akt pathways in mini-pigs
    Cheng Hsu Yang
    Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
    J Atheroscler Thromb 20:9-22. 2013
    This study tested the hypothesis that tacrolimus therapy limited left ventricular (LV) infarct and remodeling by suppressing the inflammatory response, oxidative stress and regulating the mitogen-activated protein kinase (MAPK) and Akt ..
  46. pmc FK506 biosynthesis is regulated by two positive regulatory elements in Streptomyces tsukubaensis
    Dusan Goranovic
    Acies Bio d, O, O, Tehnoloski Park 21, SI 1000, Ljubljana, Slovenia
    BMC Microbiol 12:238. 2012
    FK506 (Tacrolimus) is an important immunosuppressant, produced by industrial biosynthetic processes using various Streptomyces species...
  47. pmc Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents
    Yervand Eduard Karapetyan
    Department of Infectious Diseases, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA
    Proc Natl Acad Sci U S A 110:7044-9. 2013
    ..We screened a collection of drugs approved for human use and identified astemizole and tacrolimus, which reduced cell-surface PrP and inhibited prion replication in neuroblastoma cells...
  48. ncbi Ten-year results of a randomized trial comparing tacrolimus versus cyclosporine a in combination with mycophenolate mofetil after heart transplantation
    Sonja Guethoff
    DepDepartment of Cardiac Surgery, University of Munich, Marchioninistr 15, 81377 Munchen, Germany
    Transplantation 95:629-34. 2013
    Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after heart transplantation (HTX) are rarely ..
  49. pmc Dosing equation for tacrolimus using genetic variants and clinical factors
    Chaitali Passey
    Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
    Br J Clin Pharmacol 72:948-57. 2011
    To develop a dosing equation for tacrolimus, using genetic and clinical factors from a large cohort of kidney transplant recipients. Clinical factors and six genetic variants were screened for importance towards tacrolimus clearance (CL/F)...
  50. ncbi Impact of the CYP3A4*1G polymorphism and its combination with CYP3A5 genotypes on tacrolimus pharmacokinetics in renal transplant patients
    Masatomo Miura
    Akita University School of Medicine, 1 1 1 Hondo, Akita 010 8543, Japan
    Pharmacogenomics 12:977-84. 2011
    b>Tacrolimus is a substrate of CYP3A4 and CYP3A5. The present study investigated the impact of the CYP3A4*1/*1G polymorphism compared with CYP3A5 genotypes on the dose-adjusted pharmacokinetics of tacrolimus...
  51. pmc Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506): in vitro characterization and improved corneal permeation
    Yikang Dai
    Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People s Republic of China
    Int J Nanomedicine 8:1921-33. 2013
    ..study was to investigate the potential of liposomes containing bile salts as an ophthalmic delivery system for tacrolimus to improve corneal permeability...
  52. ncbi A topical combination of rapamycin and tacrolimus for the treatment of angiofibroma due to tuberous sclerosis complex (TSC): a pilot study of nine Japanese patients with TSC of different disease severity
    M Wataya-Kaneda
    Department of Dermatology, Graduate School of Medicine, Osaka University, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
    Br J Dermatol 165:912-6. 2011
    ..Although rapamycin improves many TSC lesions, significant side-effects appear after systemic administration. Topical administration has been recommended...
  53. ncbi The P450 oxidoreductase *28 SNP is associated with low initial tacrolimus exposure and increased dose requirements in CYP3A5-expressing renal recipients
    Hylke de Jonge
    Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Herestraat 49, B 3000 Leuven, Belgium
    Pharmacogenomics 12:1281-91. 2011
    ..Because tacrolimus is metabolized by CYP3A isoenzymes, this SNP might affect tacrolimus pharmacokinetics.
  54. ncbi Systemic ciclosporin and tacrolimus in dermatology
    V Madan
    The Dermatology Center, University of Manchester, Hope Hospital, Salford, Manchester, UK
    Dermatol Ther 20:239-50. 2007
    Ciclosporin and tacrolimus are calcineurin inhibiting immunosuppressant agents useful in the treatment of immune-mediated inflammatory dermatoses...
  55. ncbi 12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus
    Gary Levy
    University Health Network, Toronto General Hospital, Toronto, ON, Canada
    Liver Transpl 12:1464-72. 2006
    ..microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months ..
  56. ncbi A prospective randomized trial comparing tacrolimus and steroids with tacrolimus monotherapy in liver transplantation: the impact on recurrence of hepatitis C
    Carlos Margarit
    Liver Transplantation Unit, Department of General Surgery, Hospital Vall Hebron, Universidad Autonoma Barcelona, Barcelona, Spain
    Transpl Int 18:1336-45. 2005
    The aim of this prospective randomized trial was to study the efficacy and safety of tacrolimus monotherapy (TACRO) and compare it with our standard treatment of tacrolimus plus steroids (TACRO + ST) after liver transplant (LT)...
  57. ncbi Calcineurin inhibitor minimization in the Symphony study: observational results 3 years after transplantation
    H Ekberg
    Lund University, Malmo, Sweden
    Am J Transplant 9:1876-85. 2009
    ..at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low-dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with ..
  58. pmc Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506)
    Biagio De Angelis
    Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, Houston, TX 77030, USA
    Blood 114:4784-91. 2009
    ..b>Tacrolimus (FK506) is one of the most widely used immunosuppressive agents in SOT recipients, and its immunosuppressive ..
  59. ncbi UGT1A9 -275T>A/-2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients
    R H N Van Schaik
    Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam, The Netherlands
    Clin Pharmacol Ther 86:319-27. 2009
    ..b>Tacrolimus-treated patients who were UGT1A9 -275T>A and/or -2152C>T carriers displayed a 20% lower MPA area under the ..
  60. ncbi Topical pimecrolimus in the treatment of vitiligo
    Barbara Boone
    Department of Dermatology, University Hospital of Ghent, De Pintelaan 185, 9000 Ghent, Belgium
    Eur J Dermatol 17:55-61. 2007
    ..Most clinical vitiligo trials have been performed with tacrolimus and show beneficial effects...
  61. pmc Biosynthesis of the allylmalonyl-CoA extender unit for the FK506 polyketide synthase proceeds through a dedicated polyketide synthase and facilitates the mutasynthesis of analogues
    Sangjoon Mo
    Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120 750, Republic of Korea
    J Am Chem Soc 133:976-85. 2011
  62. ncbi Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation
    T Hautz
    Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Innsbruck Medical University, Innsbruck, Austria
    Am J Transplant 10:1200-9. 2010
    ..alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 +/- 1)...
  63. pmc Origin of the allyl group in FK506 biosynthesis
    Dusan Goranovic
    Acies Bio d o o, Tehnoloski Park 21, SI 1000 Ljubljana, Slovenia
    J Biol Chem 285:14292-300. 2010
    FK506 (tacrolimus) is a secondary metabolite with a potent immunosuppressive activity, currently registered for use as immunosuppressant after organ transplantation...
  64. ncbi Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study
    Raimund Margreiter
    Department of Transplant Surgery, University Hospital Innsbruck, Anichstrasse 35, A 6020 Innsbruck, Austria
    Lancet 359:741-6. 2002
    In previous comparative studies tacrolimus was superior to the standard formulation of ciclosporin in preventing acute rejection after renal transplantation...
  65. pmc A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL)
    Michael A Pulsipher
    Division of Hematology Blood and Marrow Transplant, Primary Children s Medical Center, University of Utah School of Medicine, Salt Lake City, UT 84132 2408, USA
    Br J Haematol 147:691-9. 2009
    ..We hypothesized that the addition of sirolimus to a tacrolimus/methotrexate graft-versus-host disease (GVHD) prophylaxis regimen would decrease relapse after haematopoietic ..
  66. ncbi Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens
    Corey Cutler
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Biol Blood Marrow Transplant 11:383-8. 2005
    ..GVHD prophylaxis consisted of sirolimus/tacrolimus (ST) in the study group and tacrolimus/methotrexate (TM) in the control group...
  67. ncbi Inhibition of scratching behavior associated with allergic dermatitis in mice by tacrolimus, but not by dexamethasone
    Naoki Inagaki
    Department of Pharmacology, Gifu Pharmaceutical University, 5 6 1 Mitahorahigashi, Gifu 502 8585, Japan
    Eur J Pharmacol 546:189-96. 2006
    ..2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse skin, and comparatively examined the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior...
  68. ncbi FK506 promotes melanocyte and melanoblast growth and creates a favourable milieu for cell migration via keratinocytes: possible mechanisms of how tacrolimus ointment induces repigmentation in patients with vitiligo
    C C E Lan
    Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
    Br J Dermatol 153:498-505. 2005
    ..Topical tacrolimus (FK506) ointment has recently been added to the armamentarium against this pigmentary disorder...
  69. ncbi Factors contributing to acute rejection in renal transplantation: the role of noncompliance
    P E Morrissey
    Division of Organ Transplantation and Medical Statistics, Rhode Island Hospital, Brown Medical School, 593 Eddy Street APC 921, Providence, RI 02903, USA
    Transplant Proc 37:2044-7. 2005
    ..There was a trend toward fewer episodes of acute rejection with thymoglobulin induction and tacrolimus-based immunosuppression. Younger recipients had an increased risk of acute rejection (odds ratio 0.47, range 0...
  70. ncbi Cyclosporine versus tacrolimus treated liver transplant recipients with chronic hepatitis C: outcomes analysis of the UNOS/OPTN database
    W D Irish
    Health Outcomes Research and Biostatistics, CTI Clinical Trial and Consulting Services, Raleigh, NC, USA
    Am J Transplant 11:1676-85. 2011
    ..Recent studies suggest that outcomes may be better with cyclosporine (CSA-ME) compared to tacrolimus (TAC), but the data are inconclusive...
  71. ncbi Optimization of initial tacrolimus dose using pharmacogenetic testing
    E Thervet
    Department of Renal Transplantation, Assistance Publique Hopitaux de Paris, Necker Enfants Malades Hospital, Paris, France
    Clin Pharmacol Ther 87:721-6. 2010
    ..studies have demonstrated that patients who are expressors of cytochrome P4503A5 (CYP3A5) require a higher tacrolimus dose to achieve a therapeutic trough concentration (C(0))...
  72. pmc Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation
    Corey Cutler
    Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 109:3108-14. 2007
    We assessed the combination of sirolimus and tacrolimus without methotrexate after myeloablative allogeneic stem cell transplantation from 53 matched related donors (MRDs) and 30 unrelated donors (URDs)...
  73. ncbi Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus
    Varun Garg
    Clinical Trials and Medical Information, Vertex Pharmaceuticals Inc, Cambridge, MA 02139, USA
    Hepatology 54:20-7. 2011
    ..is an inhibitor of the enzyme cytochrome P450 3A, responsible for the metabolism of both cyclosporine and tacrolimus. This Phase I, open-label, nonrandomized, single-sequence study assessed the effect of telaprevir ..
  74. ncbi Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug
    Alexander Kapp
    Department of Dermatology and Allergology, Hannover Medical University, Ricklingerstrasse 5, D 30449 Hannover, Germany
    J Allergy Clin Immunol 110:277-84. 2002
    ..In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control...
  75. pmc Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei
    Chiatogu Onyewu
    Departments of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Antimicrob Agents Chemother 47:956-64. 2003
    ..The calcineurin inhibitors cyclosporine A (CsA) and tacrolimus (FK506) are dramatically synergistic with azoles, resulting in potent fungicidal activity, and mutant strains ..
  76. ncbi A new cell-permeable peptide allows successful allogeneic islet transplantation in mice
    Hirofumi Noguchi
    Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2 5 1 Shikata cho, Okayama, 700 8558 Japan
    Nat Med 10:305-9. 2004
    ..In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically...
  77. ncbi Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation
    Lionel Rostaing
    Multiorgan Transplant Unit, Rangueil University Hospital, 31059 Toulouse, France
    Transplantation 79:807-14. 2005
    ..We investigated whether a corticosteroid-free tacrolimus (Tac)/mycophenolate mofetil (MMF) regimen, in combination with daclizumab (Dac) induction therapy, provides ..
  78. ncbi Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics
    Kazuhide Iwasaki
    Department of Pharmacokinetics Dynamics Metabolism, Pfizer Global Research Development, Nagoya Laboratories, Pfizer Japan Inc, Aichi, Japan
    Drug Metab Pharmacokinet 22:328-35. 2007
    b>Tacrolimus (FK506), an immunosuppressive drug, is co-medicated with multiple drugs under clinical conditions. Tacrolimus is highly lipophilic and is excreted from the body after receiving extensive metabolism...
  79. ncbi Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus
    F Vincenti
    University of California San Francisco Kidney Transplant Service, San Francisco, CA, USA
    Am J Transplant 7:1506-14. 2007
    DIRECT (Diabetes Incidence after Renal Transplantation: Neoral C(2) Monitoring Versus Tacrolimus) was a 6-month, open-label, randomized, multicenter study which used American Diabetes Association/World Health Organization criteria to ..
  80. ncbi A new functional CYP3A4 intron 6 polymorphism significantly affects tacrolimus pharmacokinetics in kidney transplant recipients
    Laure Elens
    Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands
    Clin Chem 57:1574-83. 2011
    b>Tacrolimus (Tac) is a potent immunosuppressant with considerable toxicity. Tac pharmacokinetics varies between individuals and thus complicates its use in preventing rejection after kidney transplantation...
  81. ncbi Tacrolimus enhances transforming growth factor-beta1 expression and promotes tumor progression
    Mary Maluccio
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Transplantation 76:597-602. 2003
    ..Transforming growth factor (TGF)-beta(1) has been associated with tumor invasion and metastasis, and we have implicated cyclosporine-associated TGF-beta(1) hyperexpression in tumor progression in mice...
  82. ncbi Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors: reassessment of risk factors for tumor recurrence
    Marco Vivarelli
    Department of Surgery and Transplantation, University of Bologna, S Orsola Hospital, Via Massarenti 9, Bologna, Italy
    Ann Surg 248:857-62. 2008
    We assessed the effect of tacrolimus on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) and compared it with that of the other calcineurin inhibitor, cyclosporine.
  83. ncbi Susceptibility of human mesenchymal stem cells to tacrolimus, mycophenolic acid, and rapamycin
    Martin J Hoogduijn
    Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
    Transplantation 86:1283-91. 2008
    ..The molecular targets of these drugs are expressed in MSC, but the effect of their inhibition on MSC functioning is unknown...
  84. pmc Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients
    B R Allen
    Department of Dermatology, University Hospital, Nottingham, UK
    Arch Dis Child 88:969-73. 2003
    ..To measure pimecrolimus blood concentrations and to evaluate tolerability and efficacy in children and infants treated topically for atopic dermatitis with pimecrolimus cream 1% for three weeks...
  85. ncbi Cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC-restricted antigen presentation pathways in dendritic cells
    Young Ran Lee
    College of Pharmacy, Chungbuk National University, Cheongju 361 763, South Korea
    Blood 105:3951-5. 2005
    The main targets for the immunosuppressive calcineurin inhibitors, cyclosporin A (CsA) and tacrolimus, have been considered to be activated T cells, but not antigen-presenting cells...
  86. ncbi Structural organization of a multifunctional polyketide synthase involved in the biosynthesis of the macrolide immunosuppressant FK506
    H Motamedi
    Dept of Natural Products Drug Discovery, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    Eur J Biochem 244:74-80. 1997
    ..Disruption of fkbA results in the generation of an FK506 non-producing mutant demonstrating direct involvement of fkbA in the biosynthesis of FK506...
  87. pmc Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition
    Giulio Taglialatela
    Department of Neurosciences and Cell Biology, The University of Texas Medical Branch at Galveston, TX 77555, USA
    Behav Brain Res 200:95-9. 2009
    ..In human AD, CaN inhibition may lead the way for therapeutics to improve declarative memory performance as demonstrated in a mouse model for AD...
  88. ncbi Inhibition of human insulin gene transcription by the immunosuppressive drugs cyclosporin A and tacrolimus in primary, mature islets of transgenic mice
    Elke Oetjen
    Department of Molecular Pharmacology, Robert Koch Strasse 40, 37075 Gottingen, Germany
    Mol Pharmacol 63:1289-95. 2003
    Cyclosporin A and tacrolimus are clinically important immunosuppressive drugs. They share a diabetogenic action as one of their most serious adverse effects. The underlying mechanism is unknown...
  89. ncbi Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease
    D R Couriel
    Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
    Br J Haematol 130:409-17. 2005
    ..We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid-resistant cGVHD...
  90. pmc Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data
    Angela C Webster
    Cochrane Renal Group, Centre for Kidney Research, Children s Hospital at Westmead, Westmead, NSW 2145, Australia
    BMJ 331:810. 2005
    To compare the positive and negative effects of tacrolimus and ciclosporin as initial treatment for renal transplant recipients.
  91. ncbi Atopic keratoconjunctivitis and atopic dermatitis
    Stefano Guglielmetti
    Moorfields Eye Hospital, NHS Foundation Trust, London UK
    Curr Opin Allergy Clin Immunol 10:478-85. 2010
  92. ncbi Systematic review and metaanalysis of the efficacy of FK506 in experimental stroke
    Malcolm R Macleod
    National Stroke Research Institute, Melbourne, Australia
    J Cereb Blood Flow Metab 25:713-21. 2005
    ..These findings show a substantial efficacy for FK506 in experimental stroke, but raise concerns that our estimate of effect size might be too high because of factors such as study quality and possible publication bias...
  93. ncbi Inhibitors of the calcineurin/NFAT pathway
    Sara Martínez-Martínez
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas CSIC Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, Spain
    Curr Med Chem 11:997-1007. 2004
  94. ncbi Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors
    R A Nash
    Clinical Research Division, Fred Hutchinson Cancer Research Center, and the Department of Medicine, University of Washington, Seattle, WA, USA
    Blood 96:2062-8. 2000
    ..b>Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was effective in combination with ..
  95. ncbi RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs
    D M Sabatini
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    Cell 78:35-43. 1994
    ..We propose that RAFT1 is the direct target of FKBP12-rapamycin and a mammalian homolog of the TOR proteins...
  96. ncbi Calcineurin inhibitor nephrotoxicity
    Maarten Naesens
    Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Herestraat 49, B 3000 Leuven, Belgium
    Clin J Am Soc Nephrol 4:481-508. 2009
    The use of the calcineurin inhibitors cyclosporine and tacrolimus led to major advances in the field of transplantation, with excellent short-term outcome...
  97. ncbi FK506 can activate transforming growth factor-beta signalling in vascular smooth muscle cells and promote proliferation
    Arturo Giordano
    Invasive Cardiology Unit, Clinica Pineta Grande, Castelvolturno, Italy
    Cardiovasc Res 79:519-26. 2008
    ..We investigated the effect of FK506, also known as tacrolimus, on cellular proliferation and on matrix protein production in human VSMCs.
  98. ncbi Dermatophagoides farinae extract induces severe atopic dermatitis in NC/Nga mice, which is effectively suppressed by the administration of tacrolimus ointment
    Tomoyuki Oshio
    Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo, Japan
    Int Immunopharmacol 9:403-11. 2009
    ..Interestingly, repeated application of tacrolimus ointment potently inhibited DfE-induced atopic dermatitis in NC/Nga mice concomitant with the inhibition of ..
  99. ncbi Treatment with twice-weekly tacrolimus ointment in patients with moderate to severe atopic dermatitis: results from two randomized, multicentre, comparative studies
    Sakari Reitamo
    Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
    J Dermatolog Treat 21:34-44. 2010
    Twice-weekly tacrolimus ointment for mild to severe atopic dermatitis (AD) significantly reduced the number of flares and prolonged flare-free intervals compared with standard treatment in the CONTROL studies.
  100. pmc Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes
    Qing Huai
    Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 7260, USA
    Proc Natl Acad Sci U S A 99:12037-42. 2002
    ..The comparison of CyPA-CsA-CN with FKBP-FK506-CN significantly contributes to understanding the molecular basis of regulation of CN activity by the immunophilin-immunosuppressant...
  101. ncbi AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients
    Eduard M Scholten
    Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
    Kidney Int 67:2440-7. 2005
    b>Tacrolimus has a narrow therapeutic window, and bioavailability is known to vary considerably between renal transplant recipients...

Research Grants68

  1. Inhibition of IkK to treat lethal Graft-vs.-Host Disease
    Patrick Flood; Fiscal Year: 2009
    ..Experiments are proposed to evaluate the combination of TLX1001 with the calcineurin inhibitor tacrolimus. Finally, studies are proposed to investigate the pharmacokinetics and pharmacodynamics of the compound in dogs ..
  2. Novel Macrolide Th17 Inhibitors
    Jay K Kolls; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Interleukin-17 can cause lung inflammation and asthma. This project is to indentify drugs that can inhibit IL-17 and lung inflammation. ..
  3. Deriving hepatocytes from disease specific iPS to treat metabolic liver disorders
    Namita Roy-Chowdhury; Fiscal Year: 2013
    ..Gunn rats will be treated with a tacrolimus-based immunosuppressive regimen that has been shown to prevent the rejection of xenografted human hepatocytes in ..
  4. The Role of FKBP10 in Recessive Osteogenesis Imperfecta
    Caressa Lietman; Fiscal Year: 2013
    ..The National Institute of Dental and Craniofacial Research is the recipient organization of this fellowship because OI and Bruck syndrome are characterized by craniofacial phenotypes. ..
  5. SFRP2 and NFAT are therapeutic targets in angiosarcoma
    NANCY K DEMORE; Fiscal Year: 2013
    ..b>Tacrolimus (FK506) is an immunosuppressive drug that binds to the immunophlin FKBP12 in lymphocytes...
  6. Dysfunctional PGC-1alpha expression in skeletal muscle during diabetes
    S Russ Price; Fiscal Year: 2013
    ..Use of Cn inhibitors could have a negative impact on both types of patients. Lastly, our results could be broadly applicable to Veterans suffering from many types of debilitating diseases associated with atrophy. ..
  7. Depot calcineurin inhibitors to prevent graft rejection
    Thomas J Smith; Fiscal Year: 2010
    ..Substantial inter-and intra-patient variability of the calcineurin inhibitors cyclosporine A (CsA) and tacrolimus (Tac) means that even frequent drug monitoring cannot eradicate rejection due to sub- therapeutic troughs or ..
  8. Developing a New Therapeutic for the Treatment of Invasive Aspergillosis
    Mitchell W Mutz; Fiscal Year: 2013
    ..fumigatus wild-type and antifungal resistant strains, potentially transforming the treatment paradigm for IA. ..
  9. A Clinical Trial to Prevent New Onset Diabetes After Transplantation
    Akinlolu O Ojo; Fiscal Year: 2013
    ..resistance and hepatic gluconeogenesis;(3) direct beta-cell injury by the calcineurin inhibitor (cyclosporine or tacrolimus) and;(4) increased dietary caloric load secondary to the abrogation of chronic uremia-related anorexia...
  10. Pharmacogenomics of Tacrolimus and New Onset Diabetes After Kidney Transplant
    Kelly A Birdwell; Fiscal Year: 2013
    ..in transplant pharmacogenomics focused on the underlying genetic factors that affect individual variation in tacrolimus disposition and toxicities, particularly in relation to abnormal glucose metabolism and new onset diabetes after ..
  11. A cell-specific inducible model of hearing loss
    Albert S Edge; Fiscal Year: 2011
    ..Because of the clear correlation between loss of cochlear cells and sensorineural hearing loss, improvements in our ability to regenerate these cells will lead directly to new treatments for loss of hearing. ..
  12. L-arginine supplement for the prevention of calcineurin inhibitor nephrotoxicity
    W Ray Kim; Fiscal Year: 2011
    ..insufficiency is most commonly a result of long term exposure to calcineurin inhibitors, namely cyclosporine and tacrolimus, used to prevent and treat rejection...
  13. The role of intracellular trafficking pathways in calcium signaling
    Suzette Farber-Katz; Fiscal Year: 2013
    ..The characterization of these proteins will lead to the elucidation of novel pathways that control calcium signaling. ..
    JEFFREY SCOTT BARRETT; Fiscal Year: 2010
    ..Drug dashboard prototypes for methotrexate (chemotherapeutic agent) and tacrolimus (used to prevent organ rejection) are under development and will be clinically evaluated prior to a production ..
  15. Novel Antifungal Therapeutic Approaches
    Joseph Heitman; Fiscal Year: 2012
    ..The goal is to harness signaling cascades to develop novel antifungal therapies. ..
  16. Role of Ca2+/Calcineurin Signaling in S. cerevisiae
    Martha S Cyert; Fiscal Year: 2013
    ..Preliminary observations suggest roles for CN and Whi3 in yeast stress granules, which form in response to glucose starvation and contain non-translating mRNAs complexed with initiation factors. ..
  17. Ryanodine receptor in cardiac hypertrophy and heart failure
    GERHARD W MEISSNER; Fiscal Year: 2013
    ..Our studies will provide new approaches to minimize the risks of cardiac hypertrophy and heart failure, one of the most frequent causes of death in humans. ..
  18. Phase II Trial of Vorinostat plus Tacrolimus and Mycophenolate to Prevent GVHD
    Sung Choi; Fiscal Year: 2013
    ..A novel preventive strategy to mitigate GVHD will allow for better harnessing of this effective therapeutic modality. ..
  19. Donor Stem Cells, Campath, T/B Cell Regulation In HLA-Identical Renal Transplants
    Joshua Miller; Fiscal Year: 2010
    ..This is to be accompanied by a temporary course of therapy with Tacrolimus converted to Sirolimus (Tacro-Siro conversion) to be withdrawn at 12 months, and mycophenolate mofetil (MMF) to ..
    Arthur Karlin; Fiscal Year: 2011
    ..The results will provide insights into the molecular mechanisms of allosteric interactions in these two channels and will provide molecular structural bases for cardiovascular therapeutics targeted at these channels. ..
    Jerrold R Turner; Fiscal Year: 2012
    ..In addition, the TR-FRET approach will yield robust high throughout screens to identify agents that modulate a wide variety of PPIs in live cells. ..
  22. Anti-CD47 mAb Therapy to Improve Kidney Transplantation
    PAMELA ANN TOY-MANNING; Fiscal Year: 2013
    ..in an allogeneic (Brown Norway to Lewis) rat kidney transplant model with the use of an immunosuppressive drug (tacrolimus) under SCD and DCD conditions to mimic the mismatch that occurs with human donors/recipients. Aim 2...
  23. The role of Nox2 in CNI-induced renal fibrosis
    Arjang Djamali; Fiscal Year: 2013
    ..CNIs including cyclosporine A (CsA) and tacrolimus (TAC) are the backbone of anti-rejection therapy in transplantation...
  24. Translation Regulation of Collagen-1 in Liver Fibrosis: Target of Drug Discovery
    Zarko Manojlovic; Fiscal Year: 2013
  25. Targeting CCR7 for the Prevention/Treatment of GvHD
    JONATHAN STUART SERODY; Fiscal Year: 2013
    ..acute GvHD in a haploidentical transplant model and that this activity is similar to that found using the drug tacrolimus. This proposal is focused on determining if these inhibitors and two other compounds can prevent GvHD without ..
  26. Preserving Renal Function &Protective Immunity Via Anti-LFA1-Based CNI Avoidance
    Kenneth A Newell; Fiscal Year: 2013
    ..of renal structure and function and lower rates of PTDM, hypertension, and dyslipidemia relative to a tacrolimus-based regimen...
  27. In Vivo Assessment of Calcineurin Inhibitor Toxicity in Children
    Joshua M Thurman; Fiscal Year: 2013
    ..markers established in the investigators'laboratories to assess the toxicodynamic mechanisms of the CNI tacrolimus in pediatric patients...
  28. A Combination Therapy Approach to Treating Drug Resistant Fungal Infections
    Mitchell W Mutz; Fiscal Year: 2011
  29. Role of calcineurin in store-operated calcium entry of pulmonary endothelium
    AUDREY ANNE VASAUSKAS; Fiscal Year: 2013
    ..abstract_text> ..
  30. Development of Genetic Tools in Entamoeba histolytica
    Upinder Singh; Fiscal Year: 2013
    ..In conclusion, these new genetic tools should provide more sophisticated methods of genetic manipulation and will be a great advance for the Entamoeba research community. ..
  31. Individualizing Therapy for Kidney and Heart Transplant Recipients
    PETER SCOTT HEEGER; Fiscal Year: 2013
    ..without evidence of anti-donor primed/memory T cells in their peripheral blood at 6 months will be randomized to tacrolimus elimination or remain on standard therapy...
  32. Pathology-directed combination therapy for pediatric TBI
    Ramesh Raghupathi; Fiscal Year: 2013
    ..abstract_text> ..
  33. Structural Basis of Dysfunctional Calcium Release Channels in Heart Disease
    Zheng Liu; Fiscal Year: 2013
  34. Hippocampal Synaptic Structure
    Philip W Landfield; Fiscal Year: 2013
    ..Given the dramatic increase in the aging population, it is becoming increasingly important to identify and develop such therapies to maintain cognitive function in the elderly. ..
  35. Calcineurin Phosphatase in Cell Signaling Pathways
    Chi Wing Chow; Fiscal Year: 2010
    ..understanding of the calcineurin phosphatase, which is the main target of immunosuppressants cyclosporin A and tacrolimus. PUBLIC HEALTH RELEVANCE: Cyclosporin A and tacrolimus inhibit calcineurin and reduce graft rejection in ..
  36. Bladder drug delivery using intravesical liposomes to treat overactive bladder
    JONATHAN H KAUFMAN; Fiscal Year: 2012
    ..will optimize the liposome platform technology for BoNT in comparison to a small molecular weight potent drug (tacrolimus) to achieve desired product stability of liposome formulation and shelf life that can sustain commercial use...
  37. Role of Immune Cells in Immunosuppressive Drug-Induced Hypertension
    Brett M Mitchell; Fiscal Year: 2013
    ..mechanisms by which alterations in T cells caused by the immunosuppressive drugs cyclosporine A (CsA) and FK506 (tacrolimus) alter endothelial function and blood pressure regulation...
  38. Clinical Refinement of islet transplantation
    NICOLE ANN TURGEON; Fiscal Year: 2011
    ..islet transplantation worldwide indicates that in the presence of sirolimus-based, steroid-free, low-dose tacrolimus therapy, usually more than one donor pancreas graft is required to attain insulin independence...
  39. T and B cell Homeostasis After Induction Therapy in Kidney Transplantation
    Fadi G Lakkis; Fiscal Year: 2013
    ..to Thymoglobulin induction in patients receiving identical maintenance immunosuppression (mycophenolic acid + Tacrolimus + early corticosteroid withdrawal)...
  40. Induction of Donor Tolerance in Renal Transplants
    Suzanne T Ildstad; Fiscal Year: 2012
    ..A recent meeting with FDA classified our product as Phase II, another milestone that will enhance commercialization. ..
  41. G Proteins and Opiate Receptor Functions
    Ping Yee Law; Fiscal Year: 2010
    ..Genetic alteration of the proteins levels will be carried out in mice and other models to test the effects of these proteins in chronic opiate drug actions. ..
  42. A new class of immunomodulator, CRAC channel blockers
    Yousang Gwack; Fiscal Year: 2013
    ..Such small molecule blockers targeting Orai1 activity is likely to have much less side effects than immunosuppressive drugs such as cyclosporin A and tacrolimus because the CRAC channel is specifically predominant in immune cells.
  43. Natural Product-Inspired Method for Enhancing HIV Protease Inhibitors
    Jason E Gestwicki; Fiscal Year: 2013
    ..This study is significant because it addresses an important problem in the treatment of AIDS. The proposed work is innovative because it will explore a fundamentally new, "natural product-inspired" strategy. ..
  44. Novel Therapies to Improve Renal and Cardiac Allograft Outcomes
    Anil Chandraker; Fiscal Year: 2013
    ..primary heart transplant recipients with a PRA of <10% will be randomized to conventional immunosuppression (tacrolimus, MMF and rapid steroid taper) versus induction therapy with anti-CD20 mAb (Rituxan) plus conventional ..
  45. Calcineurin and Neuropathic Pain
    Vjekoslav Miletic; Fiscal Year: 2013
    ..From a therapeutic perspective we seek better target specificity for more effective analgesic treatments. ..
  46. Structural and functional versatility of NFAT
    Lin Chen; Fiscal Year: 2013
  47. A Computer Modeling Approach to Create an Antifungal to Improve the Treatment of
    Mitchell W Mutz; Fiscal Year: 2013
    ..3. Screen and select compounds for antifungal activity against strains of C. neoformans and emerging cryptococcal species, pk/pd properties, and iterate library based on observed SAR. ..
  48. The Hsp90 cochaperone FKBP51 regulates tau structure and function
    Chad A Dickey; Fiscal Year: 2013
    ..These studies may lead to drug development that can provide sufferers of tauopathies a way to combat their condition, with the ultimate goal being a cure. ..
  49. Polyomavirus and Mentoring in Renal Transplantation
    Daniel C Brennan; Fiscal Year: 2012
    ..that the incidence of polyomavirus (BK) in the urine and blood was the same in patients randomized to receive tacrolimus or cyclosporine...
  50. Genomics of Kidney Transplantation Admin
    Arthur J Matas; Fiscal Year: 2013
    ..Proiect 2. has 4 Specific Aims. Aim 1: To identify SNPs associated with tacrolimus blood levels;Aim 2: to identify SNPs associated with early tacrolimus-related nephrotoxicity and immune ..
  51. Neuronal specific Autophagy Signaling
    Dale M Ando; Fiscal Year: 2013
  52. Communication between neighboring ryanodine receptor channels in skeletal muscle
    Julio A Copello; Fiscal Year: 2010
    ..This aim is subdivided in three sub-Aims: A) Define the role of ATP/Mg2+ in RyR1 coordination;B) Define the role of Ca2+ in coordinated gating;and C) Define the role of FKBP12 (Calstabilinl) and other ancillary proteins. ..
  53. A Randomized Trial of Tac/MTX/bortezomib vs Tac/MTXplacebo in Allogeneic HSCT
    Joseph H Antin; Fiscal Year: 2013
    ..Bortezomib in combination with tacrolimus and methotrexate (tac/mtx/bort) has been shown to be useful in preventing GVHD in a phase l/ll trial...
  54. Bone Marrow Transplant Clinical Network
    Edward A Stadtmauer; Fiscal Year: 2013
  55. Pharmacogenetics in Rural and Underserved Populations
    Kenneth E Thummel; Fiscal Year: 2013
    ..use, and other promising examples are emerging, including tests to improve the safety of warfarin, tamoxifen and tacrolimus therapy...
  56. Statins for Prevention of GVHD
    MARCO B MIELCAREK; Fiscal Year: 2013
    ..to recipients given cyclosporine (CSP)-based postgrafting immunosuppression and not observed among those given tacrolimus (TAC). These findings, if confirmed, will have a significant impact on improving the safety of clinical HCT...
  57. New Approaches to Axonal Protection After TBI
    Thomas M Reeves; Fiscal Year: 2013
    ..The long-term goal is to translate findings from these laboratory studies to the development of therapeutic strategies to improve white matter functioning specifically, and outcome of TBI generally, in human patients. ..
  58. Extracellular Matrix Mediates Axonal Integrity Following Brain Injury
    Linda L Phillips; Fiscal Year: 2013
    ..These studies are likely to identify novel options for regional and fiber targeted therapy in patients suffering from axonal damage after TBI. ..
  59. Molecular pathogenesis of calcineurin inhibitor-induced hypertension
    Chao Ling Yang; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): This project will examine how calcineurin inhibitors, such as tacrolimus and cyclosporine, cause hypertension with potassium retention...
    Monica Liebert; Fiscal Year: 1993
  61. Calcineurin in pancreatitis
    Sohail Z Husain; Fiscal Year: 2013
  62. Biomolecular Markers for Safe Minimization of Immunosuppression
    Manikkam Suthanthiran; Fiscal Year: 2013
    ..allograft nephropathy (CAN) in renal allograft recipients randomized to either a low dose or a standard dose tacrolimus regimen...
  63. Modulation of innate immunity in lung transplantation
    Sadis Matalon; Fiscal Year: 2005
    ..by Fujisawa Healthcare, Inc, was planned to compare the efficacy of treating lung transplant patients with tacrolimus and sirolimus versus tacrolimus and azathioprine in reducing the incidence of acute rejection during the first ..
  64. Sustained release calcineurin inhibitors for the prevention of graft rejection
    Thomas Smith; Fiscal Year: 2007
    ..the calcineurin inhibitors by developing sustained release subcutaneous injectable formulations for the drugs tacrolimus and cyclosporine...
  65. Pre-clinical Studies on Lupinus termis Seeds Extract
    MIKHAIL ANTOUN; Fiscal Year: 2003
    ..Aside from Protopic (tacrolimus) ointment, which has been recently approved by the FDA, the main treatment for the past 40 years has been ..
    Mitchell Chesler; Fiscal Year: 2000
    ..Water movements will be investigated in slices from aged animals. The role of the Na:HCO3 cotransport will be assessed. Light scattering and Na-K changes will be compared with wet-dry weight and tracer measurements. ..
    WHYTE OWEN; Fiscal Year: 2002
    ..The possibility that calcineurin phosphatase activity may be regulated by the cellular redox provides a link between oxidative stress and calcium- dependent signal transduction pathways. ..
    Frederick Grinnell; Fiscal Year: 2002