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 nonmyeloablative conditioning) at D 15 -D 25 (all participants) and D 40 -D 80 (participants with myeloablative conditioning). The CsA AUC 0À4h , AUC 0À8h and AUC 0À12h 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 0À4h (r 2 ¼ 0.15), AUC 0À8h (r 2 ¼ 0.21) and AUC 0À12h (r 2 ¼ 0.53). C2 was better correlated with AUC 0À4h (r 2 ¼ 0.88), AUC 0À8h (r 2 ¼ 0.76) and AUC 0À12h (r 2 ¼ 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.

Correlation between Cyclosporine Blood Levels and Area under Blood Concentration Time Curve in Iraqi Bone Marrow Transplant Patients Treated with Neoral® Oral Solution

“…Therefore, C2 represents the optimal sampling time point which reflects the total systemic exposure (AUC) and consequently the optimal effect and adverse effect of the drug. Interestingly, the best correlations between C2 with AUC 0-12h and C2 with AUC 0-4h , in addition to the poor correlation of both AUCs with C0 found in the current investigation for bone marrow transplant Iraqi patients (Table 4) are similar to the results obtained in studies conducted in other nations and for different types of organ transplantation [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34].…”

“…Interestingly, several articles demonstrated the best correlation between C2 and AUC 0-4h in different nations and for different types of organs allograft. Among these studies, were reported for lung transplantation [22], liver transplant recipients [24], heart transplantation [21,25], allogeneic stem cell transplantation [26], for children with idiopathic nephrotic syndrome [27], and for other types of organs transplantations [23,28]. The best correlation was also found between cyclosporine C2 level and AUC0-6hr for patients with corticosteroid resistant systemic lupus erythematosus [29].…”

Prediction of Area under the Cyclosporine Concentration Versus Time Curve in Children Undergoing Hematopoietic Stem Cell Transplantation

“…Several investigators have reported cyclosporine AUC in HSCT patients after i.v. administration [3,[10][11][12][13][14][16][17][18][19]26,27]. The method used to calculate or estimate cyclosporine AUC was not described in some of these reports [13], and serum rather than whole blood concentrations (the accepted standard matrix) were reported in another [10].…”

“…Cyclosporine dose adjustment based on AUC rather than C 0 has consequently become the standard of care. This approach has only just begun to be evaluated in HSCT [10][11][12][13][14][15][16][17][18][19]. Classical determination of AUC entails a large total blood sample volume, high workload to obtain the samples, high assay costs, and potentially a high level of patient inconvenience or distress.…”