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Specimen Dilution for C2 Monitoring with the Abbott TDxFLx Cyclosporine Monoclonal Whole Blood Assay

¹ ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories Inc., Salt Lake City, UT;² Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT

^aaddress correspondence to this author at: ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories Inc., 500 Chipeta Way, Salt Lake City, UT 84108; fax 801-584-5207, e-mail juenkejm@aruplab.com

The first 300 words of the full text of this article appear below.

Cyclosporine (CsA), a hydrophobic cyclic undecapeptide produced by the fungus Tolypocladium inflatum, is composed of 11 amino acid residues. As a calcineurin inhibitor, CsA inhibits cytokines such as interleukin-2 at the early stage of T-lymphocyte activation. CsA has been shown to improve graft survival in skin, heart, kidney, pancreas, bone marrow, lung, small intestine, and liver transplants (1)(2), but the use of CsA is associated with serious toxic side effects, primarily nephrotoxicity and hepatotoxicity. Other adverse effects include diarrhea, gingival hyperplasia, nausea, vomiting, hirsutism, tremor, and hypertension. CsA is extensively metabolized, and at least 20 metabolites have been identified, the majority of which are considered to be therapeutically inactive (1)(2)(3)(4).

CsA monitoring is performed with fluorescence polarization immunoassay, enzyme-based Emit® immunoassays, and chromatographic (HPLC) and tandem mass spectrometry techniques (5)(6)(7)(8)(9). Immunoassay techniques have variable cross-reactivities with CsA metabolites, producing overestimated concentrations of CsA in whole blood. Nevertheless, immunoassays offer rapid turnaround times and technical ease and are therefore the most commonly used analytical methods. In a recent College of American Pathologist study, 247 of 292 respondents used the Abbott TDxFLx CsA monoclonal whole blood assay (fluorescence polarization immunoassay) (10)(11).

The process of optimizing immunosuppressant dosing with therapeutic drug monitoring continues to be refined, particularly for CsA. Current evidence suggests that a single concentration of CsA determined with a specimen collected 2 h postdose (C2) better reflects the area under the curve than a conventional predose (trough) concentration, particularly when the microemulsion formulation is used (12). Clinical outcome studies suggest that adjusting the dose on the basis of C2 values may be preferred to adjusting dose on the basis of trough values. . . . [Full Text of this Article]