Comparison of neoral dose monitoring with cyclosporine trough levels versus 2-hr postdose levels in stable liver transplant patients

Background. We reported that cyclosporine 2-hr postdose levels (C-2) correlate better with the AUC(0-4 hr) than trough levels (C-0) in heart transplant patients receiving Neoral. Methods. We compared Neoral dose adjustment with C-0 (group 1: 100-200 ng/ml) vs. C-2 (group 2: 700-1000 ng/ml; group 3: 300-600 ng/ml) in 35 stable adult patients >1 year after liver transplantation. The AUC(0-4 hr) was calculated, and simultaneous blood samples were obtained to measure calcineurin inhibition, Clinical benefit was defined as the absence of rejection; and no increase in serum creatinine at the 7-month follow-up. Results. C-2 correlated better with the AUC(0-4 hr) than C-0 (r=0.92 vs. r=0.40). Neoral dose increased by 17% and 39% in groups 1 and 2, and decreased by 18% in group 3 (P=0.002 vs. group 1 and P=0.0004 vs. group 2), Serum creatinine increased by 2.1% and 16% in groups 1 and 2, and decreased by 5.1% in group 3 (P=0.006 vs. group 2), A clinical benefit was observed in 37.5%, 23%, and 82% of patients in groups 1, 2, and 3 (P=0.03 vs. group 1 and P=0.01 vs. group 2), Calcineurin inhibition was similar in all groups at 2-hr (44+/-17%, 39+/-30%, and 44+/-35%), in spite of different Neoral doses (2.9+/-0.9, 4.0+/-1.8, and 2.6+/-1.3 mg/kg/day) and C-2 (857+/-226, 922+/-274, and 588+/-274 ng/ml). Conclusions. C-2 correlated better with the AUC(0-4 hr) than C-0. Neoral dose monitoring with a C-2 range of 300-600 ng/ml resulted in a lower dose and greater clinical benefit compared to C-0 or a higher C-2 in stable liver transplant patients. The correlation between calcineurin inhibition and clinical events deserves further research.