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
Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study.
TL;DR: Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile.
Journal ArticleDOI
Tacrolimus: a further update of its use in the management of organ transplantation.
TL;DR: The reduced incidence of rejection episodes in renal transplant recipients receiving tacrolimus translated into a better cost effectiveness relative to cyclosporin microemulsion treatment, which was reflected in improved cost effectiveness.
Journal ArticleDOI
Neoral monitoring by simplified sparse sampling area under the concentration-time curve: its relationship to acute rejection and cyclosporine nephrotoxicity early after kidney transplantation.
TL;DR: The data suggest that a target AUC0-12 of 9500-11500 or AUC1-4 of 4400-5500 microg x h/L may provide optimal Neoral immunosuppression and early AUC based on PK0-4 is more closely associated with AR and CsANT than is C0.
Journal ArticleDOI
The temporal profile of calcineurin inhibition by cyclosporine in vivo.
TL;DR: CsA induces partial CN inhibition that varies directly with the blood and tissue levels, and may be greater in some tissues due to higher drug accumulation, relevant to nephrotoxicity.
Journal ArticleDOI
Relationship of FK506 whole blood concentrations and efficacy and toxicity after liver and kidney transplantation
TL;DR: Therapeutic monitoring of whole blood FK506 levels may be useful for minimizing the risks of both toxicity and rejection in kidney transplant patients and for minimize the risk of toxicity in liver transplant recipients.
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