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.