MULTICENTER COMPARISON OF FIRST-GENERATION AND 2ND-GENERATION IMX TACROLIMUS MICROPARTICLE ENZYME IMMUNOASSAYS IN LIVER AND KIDNEY-TRANSPLANTATION

Tacrolimus is a potent immunosuppressive drug successfully used for ba seline and rescue immunosuppression in patients after liver and kidney transplantation. Data from several clinical trials have demonstrated the efficacy of tacrolimus in the prevention of allograft rejection, e ven at lower concentrations in the therapeutic range (5-15 mu g/L). In fact, some patients with tacrolimus levels at less than 5 mu g/L have excellent hepatic or kidney function. The limit of detection of the I Mx Tacrolimus I assay (TAC I; Abbott Laboratories, IL) is only 5 mu g/ L and that of the lower tacrolimus calibrator is 10 mu g/L. The second -generation assay uses the same monoclonal antibody and the same IMx t echnology but offers improved sensitivity, with a dynamic range from 0 mu g/L to 30 mu g/L (lower calibrator, 3 mu g/L). The aim of this mul ticenter study was to evaluate the new IMx Tacrolimus II assay (TAC II ) by assessing its precision, sensitivity, performance, and correlatio n degree relative to the IMx TAC I assay. The study was performed at t hree centers in Spain. The within-run coefficients of variation (CVs) obtained for the new assay, using each of the trilevel controls in rep licates of 20 during 3 consecutive days, were 8.06%, 4.38% and 5.09% a t 5 mu g/L, 11 mu g/L, and 22 mu g/L, respectively. The corresponding between-run CVs obtained measuring each of the three controls in dupli cate on 10 consecutive days were 9.54%, 6.38% and 5.75%. The limit of detection, with 97.5% confidence, was 1.22 mu g/L. TAC II results (Y) were compared with those from the original TAC I assay (X) analyzing 2 93 whole blood samples from liver (n = 145) and kidney (n = 148) trans plant recipients. The correlation study with patient samples (using th e Passing-Bablock method) was y = 1.056, x + 0.017, r = 0.927. No stat istically significant differences were observed between assays (TAC I versus TAC Il) in the mean values obtained far total patients (9.89 +/ - 5.42 mu g/L versus 10.49 +/- 5.63 mu g/L), liver patients (9.16 +/- 4.79 mu g/L versus 10.00 +/- 5.20 mu g/L), and kidney patients (10.62 +/- 5.87 mu g/L versus 10.98 +/- 5.99 mu g/L). The new IMx TAC II assa y demonstrated the same precision and accuracy that characterized the original assay but showed improved sensitivity to the demands of tacro limus monitoring in the lower therapeutic range of drug concentrations .