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

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Abstract
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, completeAUCis time‐consuming and expensive. For this reason, we retrospectively reviewed 131 complete 4‐hAUC(AUC0−4) performed in 34 children (mean age 10.6 ± 2 yr) in order to construct an equation to calculateAUC0−4.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 ofAUC0−4, where AUC0−4 = 424 + (2.65 × C2),R2 = 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 calculateAUC0−4.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 estimateAUC0−4. However, for values above 4,000 ng/h/mL, the formula overestimates the trapezoidalAUC0−4.The C2 equation simplifies the CsA monitoring as a result of its high predictive value and clinical feasibility.