A strategy to calculate cyclosporin A area under the time-concentration curve in pediatric renal transplantation

The complete area under the time-concentration curve (AUC ) is considered the gold standard for cyclosporin A (CsA) monitoring, particularly in pediatric kidney graft recipients who have great absorption and drug clearance variability. However, complete AUC is time-consuming and expensive. For this reason, we retrospectively reviewed 131 complete 4-h AUC (AUC (0-4) ) performed in 34 children (mean age 10.6 +/- 2 yr) in order to construct an equation to calculate AUC (0-4.) The median time after transplantation was 540 (range: 247-1,358) days. Multiple regression analysis was performed either with a single variable or with a combination of two variables. CsA blood concentration at the second hour after the oral morning dose (C2) was the best predictor of AUC (0-4) , where AUC (0-4) = 424 + (2.65 x C2), R (2) = 0.81, p < 0.001. Only the combination of C1 and C2 offered mathematical improvement over the C2 equation. The same analysis was made for pharmacokinetic curves performed earlier than 6 months (79 +/- 55 days, range 8-169 days) and after 1 yr of transplantation. In both time-periods, C2 was the best parameter to use to calculate AUC (0-4.) The equations obtained during these two time-periods were very close to the one for the whole population. Our data shows that C2 can be safely used to estimate AUC (0-4) . However, for values above 4,000 ng/h/mL, the formula overestimates the trapezoidal AUC (0-4.) The C2 equation simplifies the CsA monitoring as a result of its high predictive value and clinical feasibility.