title: A strategy to calculate cyclosporin A area under the time-concentration curve in pediatric renal transplantation.
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, complete AUC is time-consuming and expensive. For this reason, we retrospectively reviewed 131 complete 4-h AUC (AUC0-4) performed in 34 children (mean age 10.6 +/- 2 yr) in order to construct an equation to calculate AUC0-4. 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 AUC0-4, where AUC0-4 = 424 + (2.65 x 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 calculate AUC0-4. 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 AUC0-4. However, for values above 4,000 ng/h/mL, the formula overestimates the trapezoidal AUC0-4. The C2 equation simplifies the CsA monitoring as a result of its high predictive value and clinical feasibility.
authors.affiliation: Renal Transplantation Unit and Division of Central Laboratory, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. elias.david.neto@attglobal.net
authors.forename: Elias
authors.initials: E
authors.lastname: David-Neto
authors.forename: Lilian Pereira
authors.initials: LP
authors.lastname: Araujo
authors.forename: Cristiane
authors.initials: C
authors.lastname: Feres Alves
authors.forename: Nairo
authors.initials: N
authors.lastname: Sumita
authors.forename: Pascoalina
authors.initials: P
authors.lastname: Romano
authors.forename: Elisa Midori
authors.initials: EM
authors.lastname: Yagyu
authors.forename: William Carlos
authors.initials: WC
authors.lastname: Nahas
authors.forename: Luiz Estevam
authors.initials: LE
authors.lastname: Ianhez
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine