IMMUNOSUPPRESSION Evaluation of the New Heterogeneous ACMIA Immunoassay for the Determination of Whole-Blood Cyclosporine Concentrations in Bone Marrow, Kidney, Heart, and Liver Transplant Recipients E. Huet, K. Morand, B. Blanchet, A. Astier, and A. Hulin ABSTRACT Cyclosporine (CyA) has a narrow therapeutic index. Determination of CyA concentrations correlate with rejection or adverse effects like nephropathy. Cyclosporine is assayed based on either chromatographic or many different immunoenzymologic techniques. The investigators evaluated a new heterogeneous immunoassay of CyA on RxL Dimension. The pretreatment step is automatically performed in the apparatus. Linearity, intra- and interday precision, limit of quantification, dilutions, and stability of the equipment were compared with the EMIT method for patient determinations. The heterogeneous immu- noassay showed a good linearity between 0 and 500 ng/mL, and intra- and inter-day precision with a coefficient of variation below 9.2%. The investigators observed reproduc- ible and accurate dilutions of high concentrations (500 to 2000 ng/mL). The correlation with the EMIT technique was valid: ACMIA  0.964 EMIT  0.156 (r  .96) for different types of transplant (n  116). Finally, this new system improves the determination of CyA concentrations. C YCLOSPORINE (CyA, Neoral) is a potent immuno- suppressive drug used in the field of organ transplan- tation. (heart, kidney, lungs, or liver). Because CyA is a narrow therapeutic index drug, significant consequences are associated with subtherapeutic (ie, rejection) and suprath- erapeutic (eg, nephrotoxicity) concentrations. Therefore, therapeutic drug monitoring of whole-blood concentrations has been recommended to optimize CyA therapy. 1 How- ever, the optimal method for therapeutic monitoring has yet to be defined. 2 Currently, the most common method in- volves monitoring pre-dose trough concentrations; but this is not a good indicator of total drug exposure, and inter- and intraindividual variability is important. Many investiga- tors propose the use of simplified or full area under the concentration-time curve monitoring, 3,4 which is the most precise indicator of drug exposure. Cyclosporine is assayed by immunoenzymologic or chro- matographic methods. 5,6 Determination of CyA by high- From the Laboratory of Pharmacology and Toxicology, CHU Henri Mondor, 51 ave du mal de Lattre de Tassigny, 94010 Creteil Ce ´ dex, France. Address reprint requests to Dr. Anne Hulin, PharmD, PhD, Laboratory of Pharmacology and Toxicology, CHU Henri Mon- dor, 51 ave du mal de Lattre de Tassigny, 94010 Cre ´ teil Ce ´ dex, France. E-mail: anne.hulin@hmn.ap-hop-paris.fr © 2004 by Elsevier Inc. All rights reserved. 0041-1345/04/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2004.05.062 Transplantation Proceedings, 36, 1317–1320 (2004) 1317