Sampling strategy to calculate the cyclosporin-A area under the time-concentration curve

The complete area under the time-concentration curve (AUC) is considered to be the gold standard for cyclosporin-A (CyA) monitoring. However, complete AUC is time- and cost-consuming. For this reason, we reviewed 259 4-h AUC (AUC0-4) performed in 74 renal transplanted patients in order to construct an equation to calculate AUC0-4. All samples were drawn from one adult population 13 days following transplantation, in order to allow the cyclosporin metabolism to stabilize. Regression analysis was done either with each or with a combination of two variables. Cyclosporin-A blood concentration at the second hour after the oral dose (C2) was the best predictor of AUC0-4, where AUC0-4 = 451 +(2.73 x C2), R2 = 0.87, p<0.001. The combination of C1 and C2 only, offered a better mathematical improvement to the C2 equation. This equation was further validated in 33 other CyA pharmacokinetic profiles performed in eight patients who had not participated in the equation development. In this new population, the C2 equation excellently predicted the trapezoidal AUC0-4 (R2 = 0.81). Our data shows that C2 can be safely used to estimate AUC0-4. The C2 equation simplifies CyA monitoring because of its high-predictive value and clinical feasibility.