C2 monitoring: a reliable tool in pediatric renal transplant recipients

Cyclosporine (CsA) is widely used in organ transplantation. To monitor actual drug exposure, full area under the curve (AUC) is the golden standard, but it is not feasible for routine monitoring, and several abbreviated formulas have been calculated in adults (1). We confirmed the good correlation between abbreviated and full AUC in children (2). The use of serum concentration 2 hr after CsA administration (C2) was proposed in adults undergoing heart (3), renal (4), and liver (5) transplantation. CsA metabolism demonstrates peculiarities in children: Intestinal absorption is lower, and the CsA clearance is higher (6). For these reasons, in young children, it is often necessary to administer CsA three times per day. We checked the feasibility of the C2 approach in children of different ages and with different CsA administration modalities (every 8 or 12 hr). Patients who were receiving drugs known to affect CsA metabolism were excluded from this study. A total of 43 children aged 43 to 190 months were studied. Group A consisted of nine children, aged 5 to 10 years (mean 94 months; standard deviation [SD] 17), receiving CsA twice per day, in whom 46 abbreviated AUCs were obtained. Group B consisted of 27 children, aged 11 to 15 years (mean 167 months; SD 18.5), receiving CsA twice per day, in whom 184 abbreviated AUCs were obtained. Group C consisted of seven children, aged 3 to 7 years (mean 60.1 months; SD 15.5), receiving CsA every 8 hr, in whom 68 abbreviated AUCs were obtained. The AUC in patients receiving CsA twice per day was calculated on the basis of two blood samples using the following formula: AUC=195,8+(2,4*C2)+(7,7*C6) (1). For patients in group C, the AUC was calculated on the basis of three blood samples taken just before, 1 hr, and 2 hr after the administration of the drug (2). The correlation between abbreviated AUC and C2 values and age in months was evaluated through a linear regression model in each of the groups studied and in groups A and B combined. Linear regression was also used to test the correlation between abbreviated AUC and C0, C1, and C2 in group C. The correlation between AUC and C2 in groups A, B, and C is shown in Figure 1. All linear regression models fit well, as documented by the high R2 values. Because models in groups A and B were similar, we tested a linear regression model combining all the observations of the two groups together. The correlation between AUC and C2 and age R2 was 0.84. This result shows that age does not correlate with AUC, and that C2 is sufficient to predict AUC in all age groups. Figure 1: Correlation between area under the curve (AUC) and serum concentration 2 hr after cyclosporine (CsA) administration (C2) in all groups of patients: children aged 3 to 7 years receiving CsA every 8 hr (upper); children aged 5 to 10 years receiving CsA every 12 hr (middle); patients aged 10 to 15 years receiving CsA every 12 hr (lower).The resulting equation for predicting AUC is as follows: AUC=3.75×C2+1385.25. To support these results, the correlation between AUC and C0, C1, and C2 was tested in group C. In this group of children, the best fit of the model was obtained when AUC was tested with C2. Thus, these data support the reliability of this approach in young children. L. Dello Strologo C. Pontesilli G. Rizzoni A. E. Tozzi