Cyclosporin assays, metabolite cross-reactivity, and pharmacokinetic monitoring.

Abstract

The range of cyclosporin (CsA) immunoassays has become the mainstay in many therapeutic drug monitoring laboratories for delivering CsA concentration data to support clinical care of patients after transplantation. However, these assays have been criticized because of the varying degree of CsA-metabolite interferences that introduce analytical errors. The introduction of another such CsA assay (on the AXSyM analyzer) has been considered, as the manufacturer has represented it as having a low CsA-metabolite cross-reactivity profile compared with chromatographic methods. A case is presented to question how this apparent result was obtained in view of the method using the same antibody as another CsA method from the same manufacturer (fluorescence polarizaton immunoassay on the TDx analyzer) which is well known to have poor performance in regard to CsA-metabolite cross-reactivity. The implications for this problem may be even more serious as more patients are monitored using the CsA AUC strategies, rather than the traditional trough concentration approach. Such issues reinforce the need for the clinical laboratory to be critical of methods offered commercially based on scientific/pharmacologic skills.