D. W. Holt, A. Johnston
Ann Transplant 2008; 13(1): 21-21
The principle immunosuppressive drugs are classed as critical-dose drugs, relatively small changes in their concentrations in blood or plasma leading to important changes in efficacy or toxicity. As a result, there has been intense interest in the pharmacokinetics of these drugs and in relating blood or plasma concentrations to the pharmacodynamics of the drugs. An important issue for clinicians using the drug measurements as a guide to dose adjustment, is consistency over time and comparability of results between centres. The responsibility for ensuring that assay performance is monitored and, if necessary, corrective action is taken, rests with the diagnostics industry and individual laboratories. Key issues in maintaining comparability and consistency of results are calibration accuracy and reproducibility of the methods. One approach to monitoring comparative assay performance is to analyse data from blinded external proficiency testing schemes. These show that most centres use immunoassays for these measurements and that there is a tendency to concentrate on assay reproducibility, rather than absolute accuracy. This is because metabolites of the analytes of interest cross-react with the antibodies used in the immunoassays, giving rise to a broad spectrum of results, leading to the development of assay-specific target concentration ranges. This presentation will draw on data from the International Immunosuppressive Drugs Profi ciency Testing Schemes (www. bioanalytics.co.uk) to highlight the ability of the current assays to meet the changing demands of clinical practice. In particular, it will focus on recent clinical findings which suggest that the functional sensitivity for tacrolimus assays will need to improve to accommodate anticipated reductions in tacrolimus dose, and on the impact of the increasing number of centres using high-performance liquid chromatography with mass-spectrometric detection (HPLC/MS). It might be anticipated that the use of HPLC/MS would improve performance, but the data suggest that between-centre variability is relatively high, probably due to factors such as assay calibration issues and the choice of internal standards. Preliminary data on the introduction of deuterated internal standards for some of these assays will be presented. It will be concluded that the data from external proficiency testing are of value in our ongoing quest for assays which are able to match the clinical demands for optimal immunosuppressive drug therapy following transplantation.
Keywords: immunosuppressive drugs, plasma concentrations, HPLC/MS