Benefit of Neoral C2 monitoring in de novo cardiac transplant recipients receiving basiliximab induction.
BACKGROUND
For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined.


OBJECTIVE
The purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction.


METHODS
This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function.


RESULTS
The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37.


CONCLUSIONS
These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.
Cantarovich
Marcelo
M
McGill University Health Center, Montréal, Canada.
Ross
Heather
H
Arizón
José M
JM
Gómez
Miguel A
MA
Straatman
Lynn
L
Orús
Josefina
J
Alonso-Pulpón
Luis
L
Molina
Beatriz Díaz
BD
Wang
Shaohua
S
Lage
Ernesto
E
Crespo
María G
MG
Manito
Nicolás
N
Howlett
Jonathan
J
Haddad
Haissam
H
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000077552:Basiliximab; D016572:Cyclosporine / Q000097:blood* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D016019:Survival Analysis; D017741:Survivors; D013997:Time Factors
D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab