The aim of this study was to evaluate cyclosporine (CyA) absorption profiles in heart transplantation to establish the most adequate monitoring strategy and determine the optimal therapeutic range for AUC(0-4) or C2 levels. A total of 22 full pharmacokinetic studies were performed at steady-state in 22 adult heart transplant recipients (18 men, 4 women). Twelve studies were performed during the first month posttransplant (group I), and 10 studies were done after 1 month (group II). In 9 outpatients we performed an abbreviated AUC(0-4). The mean age of the patients was 49+/-15 years (range, 15-72 years), and the mean weight was 70.4+/-10.8 kg (mean, 54-98 kg). The CyA dosage had been adjusted to maintain trough levels (C0) in the putative target ranges of 200 to 400 ng/mL in group I and between 100 to 300 ng/mL in group II. Blood samples were drawn prior to and at 0.5, 1, 2, 4, 6, 8, and 12 hours after the morning dose. The CyA blood levels were measured by the AxSYM cyclosporine assay. The AUC was calculated by the trapezoidal rule. Multiple linear regression was done to evaluate the predictive ability of various limited sampling strategies. The C0 correlated poorly, either with the full AUC (r2=0.64) or the AUC(0-4) (r2=0.43), while C2 seemed to be the most accurate single predictor of drug exposure (r2=0.92 for AUC(0-12); r2=0.74 for AUC(0-4)). For both AUC(0-4) and AUC(0-12), all 2- or 3-point strategies had r2 values approaching that of the C2 value. In conclusion, C2 is a simple, fast, and accurate value to predict AUC(0-4) in routine clinical practice. Its implementation must focus on ensuring the commitment of all unit staff, thus ensuring that patients are sampled on time and minimizing the impact on workload.