Cyclosporine Monitoring with 2-hour Postdose Levels in Heart Transplant Recipients

Cyclosporine therapeutic drug monitoring based on 2-hour postdose concentration (C2) compared with conventional trough concentration (C0) can improve clinical outcomes for de novo renal and liver transplant patients. However, in heart transplant patients, published studies are limited. To determine the clinical significance of C2 compared with C0 following orthotopic heart transplantation, the authors measured CsA at C0 and C2 and estimated CsA area under the curve (AUC) using Bayesian estimation and 4 sparse sample algorithms in a cross section of 31 adult patients receiving triple-drug immunosuppression with CsA, mycophenolate mofetil (MMF), and prednisone. CsA was measured using a validated HPLC method. Endomyocardial biopsies were graded based on the ISHLT system. Mean +/- SD values for CsA dose, C0, and C2 were 4.8 +/- 1.4 mg/kg/d, 240 +/- 62 microg/L, and 1319 +/- 469 microg/L, respectively. Correlation with AUC, using different estimation algorithms, was better for C2 (r(2) = 0.79-0.99) than for C0 (r(2)= 0.11-0.52). The mean +/- SD values for C0 (microg/L) and C2 (microg/L) for rejectors (n = 3) were 215 +/- 68 and 949 +/- 204 versus 242 +/- 62 and 1359 +/- 474 for the nonrejectors (P = 0.66 and 0.12, respectively). Fisher exact test P values using the median as threshold value for C0 and C2 (234 microg/L and 1251 microg/L, respectively) were 0.6 and 0.1. Analysis of the data revealed that C0 values in rejectors have wider variability than C2. There were no rejectors among the 16 patients exceeding the C2 median value; for C0, however, there was not an easily identifiable threshold value. There is a trend for a significant relationship between C2 and the incidence of rejection, but the number of rejectors was too small to reach statistical significance. A prospective concentration-control de novo study design is recommended as the most appropriate way to fully evaluate the potential utility of C2 monitoring in heart transplant patients.