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Therapeutic drug monitoring of ciclosporin

A. Johnston, D. W. Holt

Ann Transplant 2008; 13(1): 24-24

ID: 880178

Published:


There can be no doubt that the introduction of ciclosporin for the prevention of rejection of transplanted organs, in the early nineteen eighties, revolutionised transplantation. However, the inability to define an individual's optimal ciclosporin dose, one that maximises effi cacy while at the same time minimises toxicity, has been a problem. For this reason therapeutic drug monitoring (TDM) of ciclosporin has become an established part of the routine clinical management of patients receiving the drug after organ transplantation. The use of drug concentrations as a means of optimising ciclosporin dose has evolved in a haphazard and ad hoc fashion. Initially plasma or serum blood concentrations were measured using assay techniques that were not specific for the parent compound. Over time it was realised that neither plasma nor serum were appropriate matrices as the temperature, and hence time, of separation caused major changes in the partitioning of ciclosporin into red cells. Therefore whole blood, with EDTA anticoagulation, became the matrix of choice for the measurement of the drug. At the same time, it was becoming apparent that variations in the metabolite to parent drug ratio with time after transplant, transplant type, concurrent disease and even during rejection made the use of non-specific measurements of drug concentration unreliable and a series of specific, or at least "more specific", assay methodologies were developed. Therefore measurement of ciclosporin in whole blood with a specific assay method became the agreed consensus for all transplant types. However, there is no consensus on whether for the best results a target value or range of values should be used, what the target(s) should be, how these should be adjusted to allow for transplant type, co-medication, time after transplantation, concomitant disease, race, sex etc. Added to which there is still debate about whether pre-dose (trough or C0) or another timed sample, such as two hours after drug administration (C2), or area under the concentration time-curve (AUC) result in the best patient outcomes. These questions may only be answered, and the relative merits of different sampling times decided, by prospective testing in double blind trials. Therapeutic drug monitoring, like any other medical intervention, needs to be evaluated in terms of cost-effectiveness, feasibility and clinical relevance, with the ultimate goal of improving patient and graft survival.

Keywords: thyroid cancer metestasis, Transplantation, therapeutic drug monitoring



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