Cyclosporin: revisions in monitoring guidelines and review of current analytical methods

Abstract

This article summarizes the main changes that have occurred in cyclosporin (ciclosporin) monitoring and measurement since the previous review in this journal. Cyclosporin has been reformulated to reduce variability in its absorption, leading to fewer post-transplant rejection episodes. Monitoring has mostly utilized the measurement of pre-dose blood levels of the drug, but more recently the potential benefit of using samples collected during the first few hours post-dose has been evaluated. Calculating the area under the cyclosporin concentration-time curve may be the ideal, but is not viable in the routine clinical situation and 2-h post-dose sampling seems likely to offer a practical clinical solution. Analytical methods based on high-performance liquid chromatography (HPLC) and immunoassay are available for the determination of whole blood cyclosporin concentrations. HPLC is specific but rarely used for routine monitoring, although HPLC-tandem mass spectrometry is making the technique more viable. New immunoassays have been introduced, but none are completely specific for the parent drug and all exhibit cross-reactivity towards cyclosporin metabolites. Immunoassays were originally designed for the lower cyclosporin concentrations seen in pre-dose samples, but are being evaluated and modified for determination of the higher concentrations seen 2 h post-dose.

Impact of Cyclosporine Levels on the Development of Acute Graft versus Host Disease after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

“…CsA whole-blood concentration was measured by radioimmunoassay [10] at least twice weekly during the first four weeks after transplantation. Blood samples were collected 12 hours after the prior dose, immediately before the morning dose.…”

Association between Calcineurin Inhibitor Blood Concentrations and Outcomes after Allogeneic Hematopoietic Cell Transplantation

“…During the initial study period, CSP concentrations were measured by monoclonal or polyclonal antibody assay. Starting on July, 2007, CSP concentrations were measured by high-pressure liquid chromatography (LCMSMS) [21]. For the purpose of a uniform statistical analysis, a correction factor of 0.8 has been applied to all CSP concentrations measured by monoclonal or polyclonal antibody assay to adjust the antibody assay values to the LCNSMS values.…”

Multicenter Analytical Evaluation of the Automated Electrochemiluminescence Immunoassay for Cyclosporine

“…It was soon recognized that due to variable enteral absorption and extensive metabolism (also modulated by a number of xenobiotic compounds), therapeutic drug monitoring is indispensable for immunosuppressive therapy with CsA. Consequently, a number of immunoassays and chromatographic analytical methods for monitoring CsA have been introduced over the years 1–4…”