CsA 2-h concentration correlates best with area under the concentration–time curve after allo-SCT compared with trough CsA

Abstract

The relationship between CsA levels and area under the curve (AUC) in allo-SCT recipients, and the effect of age, concomitant use of steroid and MDR-1 polymorphism on this relationship remain largely unexplored. Steady-state CsA blood concentrations at time 0 (C0), 1 (C1), 1.5 (C1.5), 2 (C2), 3 (C3), 4 (C4), 6 (C6), 8 (C8) and 12 (C12) h post oral CsA dose were taken from 27 consenting allo-SCT recipients (receiving myeloablative or non-myeloablative conditioning) at D(15)-D(25) (all participants) and D(40)-D(80) (participants with myeloablative conditioning). The CsA AUC(0-4h), AUC(0-8h) and AUC(0-12h) were determined using trapezoidal rule, and the relationships between AUCs and CsA concentrations at various time points were examined. Poor correlation was observed between C0 and AUC(0-4h) (r(2)=0.15), AUC(0-8h) (r(2)=0.21) and AUC(0-12h) (r(2)=0.53). C2 was better correlated with AUC(0-4h) (r(2)=0.88), AUC(0-8h) (r(2)=0.76) and AUC(0-12h) (r(2)=0.83). The aforementioned factors did not influence the observed relationship. CsA levels taken at 2 h post oral CsA administration may represent the optimal time point for monitoring the biological effects of calcineurin inhibitors in allo-SCT recipients.