Comparison of neoral dose monitoring with cyclosporine through levels versus 2-hr postdose levels in stable liver transplant patients.
BACKGROUND
We reported that cyclosporine 2-hr postdose levels (C2) correlate better with the AUC0-4 hr than trough levels (C0) in heart transplant patients receiving Neoral.


METHODS
We compared Neoral dose adjustment with C0 (group 1: 100-200 ng/ml) vs. C2 (group 2: 700-1000 ng/ml; group 3: 300-600 ng/ml) in 35 stable adult patients >1 year after liver transplantation. The AUC0-4hr 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
C2 correlated better with the AUC0-4 hr than C0 (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 C2 (857+/-226, 922+/-274, and 588+/-274 ng/ml).


CONCLUSIONS
C2 correlated better with the AUC0-4 hr than C0. Neoral dose monitoring with a C2 range of 300-600 ng/ml resulted in a lower dose and greater clinical benefit compared to C0 or a higher C2 in stable liver transplant patients. The correlation between calcineurin inhibition and clinical events deserves further research.
Cantarovich
M
M
Department of Medicine, Royal Victoria Hospital, McGill University Health Center, Montréal, Québec, Canada.
Barkun
J S
JS
Tchervenkov
J I
JI
Besner
J G
JG
Aspeslet
L
L
Metrakos
P
P
D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine