Tacrolimus Measurement: Building a Better Immunoassay

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Tacrolimus (formerly known as FK506) is a macrolide immunosuppressant that is used for primary immunosuppression after organ transplantation (1). The landmark work of Starzl at the University of Pittsburgh paved the way for the clinical use of tacrolimus as a primary immunosuppressant, leading to a shift away from cyclosporine use (2–4). Today, tacrolimus is used in the majority of transplant patients (5). Tacrolimus binds to several cytosolic immunophilins of importance; binding to the FK506 binding protein leads to the formation of a complex that interacts with calcium-dependent calcineurin calmodulin translocation pathways that result in prevention of T-cell activation (6). Monitoring blood tacrolimus concentrations is essential in assessing organ rejection and toxicity because of its narrow therapeutic index, wide inter- and intraindividual pharmacokinetic variability, and susceptibility to cytochrome P450–mediated drug interactions (7). Immunoassays play a major role in the analysis of many clinical laboratory analytes and in recent years have become more popular for measuring tacrolimus, replacing the mass spectrometric methods that were initially favored over the earlier immunoassay methods. Measurement of drugs by immunoassay offers the advantages of automation and ease of use (assays available around the clock 7 days a week). Furthermore, this approach does not require specialized trained staff, has the advantage of using commercially available calibrators and reagents, and permits random-access …