Therapeutic Monitoring of Calcineurin Inhibitors for the Nephrologist
TLDR
The purpose of this article is to review the current understanding of CNI pharmacokinetics and its relevance to proper dosing and monitoring of these medications and discusses the effect of adjunctive immunosuppressive agents on CNI Pharmacokinetic and dosing.Abstract:
The calcineurin inhibitors (CNI) cyclosporine and tacrolimus remain the backbone of immunosuppression for most kidney transplant recipients. Despite many years of experience, protocols that optimize efficacy with minimal toxicity remain a subject of debate. Nevertheless, studies of the pharmacokinetic properties of the CNI, particularly cyclosporine, have led to improved dosing strategies. The purpose of this article is to review the current understanding of CNI pharmacokinetics and its relevance to proper dosing and monitoring of these medications. This article also reviews the trials that have helped to define the optimal dosages and discusses the effect of adjunctive immunosuppressive agents on CNI pharmacokinetics and dosing.read more
Citations
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Journal ArticleDOI
Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference.
Pierre Wallemacq,Victor W. Armstrong,Mercè Brunet,Vincent Haufroid,David W. Holt,Atholl Johnston,Dirk Kuypers,Yannick Le Meur,Pierre Marquet,Michael Oellerich,Eric Thervet,Burkhand Toenshoff,Nas Undre,Lutz T. Weber,Ian S. Westley,Michel Mourad +15 more
TL;DR: The importance of obtaining multicenter prospective trials to assess the efficacy of alternative strategies to TAC trough concentrations is emphasized, and single time points, limited sampling strategies, and area under concentration-time curve have all been considered to determine the most appropriate sampling procedure that correlates with efficacy.
Journal ArticleDOI
Effect of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Calcineurin Inhibitors: Part II
TL;DR: Despite a strong association between the CYP3A5 6986A>G SNP and tacrolimus pharmacokinetics, there is no consistent evidence of organ rejection as a result of genotype-related under-immunosuppression, with studies showing conflicting results in regard to the main parameters of acute rejection and nephrotoxicity.
Journal ArticleDOI
Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group.
James Neuberger,Wolf O. Bechstein,Dirk Kuypers,Patrizia Burra,Franco Citterio,Sabina De Geest,Christophe Duvoux,Alan G. Jardine,Nassim Kamar,Bernhard K. Krämer,Herold J. Metselaar,Frederik Nevens,Jacques Pirenne,Manuel Rodríguez-Perálvarez,Didier Samuel,Stefan Schneeberger,Daniel Serón,Pavel Trunecka,Giuseppe Tisone,Teun van Gelder +19 more
TL;DR: In this article, the authors provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year.
Journal ArticleDOI
PharmGKB summary: cyclosporine and tacrolimus pathways.
TL;DR: Tacrolimus (FK506) and cyclosporine (cyclosporin A, CsA) are cornerstone immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection.
Journal ArticleDOI
New insights into the pharmacokinetics and pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences for therapeutic drug monitoring in solid organ transplantation
TL;DR: New insights for the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus and the antimetabolite mycophenolic acid (MPA) are highlighted and the possible consequences are discussed.
References
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Journal ArticleDOI
Tacrolimus Combined with Two Different Dosages of Sirolimus in Kidney Transplantation: Results of a Multicenter Study
Stefan Vitko,Zbigniew Wlodarczyk,Lauri Kyllönen,Z Czajkowski,Raimund Margreiter,Lars Bäckman,Ferenc Perner,Paolo Rigotti,B. Jaques,Daniel Abramowicz,Martin F. Kessler,J. Sánchez-Plumed,Lionel Rostaing,Richard Rodger,D. Donati,Y. Vanrenterghem +15 more
TL;DR: Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.
Journal ArticleDOI
The effect of food on cyclosporine absorption.
Ptachcinski Rj,Raman Venkataramanan,Rosenthal Jt,Gilbert J. Burckart,Rodney J. Taylor,Thomas R. Hakala +5 more
TL;DR: If adequate immunosuppression is achieved with lower doses of cyclosporine taken with food, significant cost savings could be realized.
Journal ArticleDOI
Pharmacodynamic monitoring of cyclosporine a in renal allograft recipients shows a quantitative relationship between immunosuppression and the occurrence of recurrent infections and malignancies.
Claudia Sommerer,Mathias H. Konstandin,Thomas J. Dengler,Jan Schmidt,Stefan Meuer,Martin Zeier,Thomas Giese +6 more
TL;DR: Recurrent infectious complications and the degree of suppression of NFAT-regulated genes by CsA in transplanted patients are correlated with the frequency of recurrent infections and malignancies in patients with five or more years of follow-up posttransplantation.
Journal ArticleDOI
Randomized, international study of cyclosporine microemulsion absorption profiling in renal transplantation with basiliximab immunoprophylaxis
Paul Keown,Paul Keown,Edward H. Cole,Edward H. Cole,N. Muirhead,N. Muirhead,T. Romanet,Franco Citterio,Lars Bäckman,D. Del Castillo,Robert Balshaw,Hans Prestele,Lyse Beauregard-Zollinger,Sophie Fornairon,Gerard Murphy,Ferenc Perner,Azemi A. Barama,E. Ancona,Tufveson,José M. Tabernero,F. Ortega,Marco Castagneto,Paolo Rigotti,G. Boschiero,P. Vialtel,G. Ancona,D. Casadei,Horvath,J. P. Wauters,P. Szenohradszky,Greg Knoll,D. Uehlinger,David Ludwin,C. Pouteil-Noble +33 more
TL;DR: Increasing information suggests that absorption profiling may be superior to trough level monitoring for optimal concentration control of cyclosporine microemulsion (NeoralTM) therapy, and that CsA exposure early post‐transplant may correlate significantly with reduced risk of acute graft rejection.
Journal ArticleDOI
A prospective, randomized clinical trial of cyclosporine reduction in stable patients greater than 12 months after renal transplantation.
Manuel Pascual,John J. Curtis,Francis L. Delmonico,Mary Lin Farrell,Winfred W. Williams,Roberto S. Kalil,P. Jones,A. Benedict Cosimi,Nina Tolkoff-Rubin +8 more
TL;DR: This study suggests that a strategy consisting of a 50% CsA reduction is safe and is not associated with the increased risk of acute rejection observed inCsA withdrawal studies, and appears to reduce cardiovascular risk factors such as hypertension and hyperlipidemia.
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