Cyclosporin A absorption profiles in children with nephrotic syndrome

A single blood concentration measurement of Neoral 2 h after administration (C2) is a new concept in therapeutic drug monitoring (TDM). In most adult patients, the concentration of cyclosporin A (CyA) peaks within 2 h after Neoral administration. Therefore, monitoring the area under the concentration-time curve over the first 4 h post-dose (AUC0–4) is considered to be the most reliable strategy for Neoral TDM. In addition, C2 is considered to be the most accurate predictor of AUC0–4, with which C2 correlates best. Thus, in adult patients, C2 monitoring is recommended as the best single-point TDM method for Neoral. However, in paediatric patients, the effectiveness of C2 monitoring is still unclear. We examined the trough concentration (C0), C1, C2, C3, and C4 of CyA in 60 patients (1 to 20 years old, mean age 7.42±0.67 years) who had nephrotic syndrome treated with Neoral. The peak concentration of C0-C4 was C1 or C2 in 38 patients (early peak group) and C3 or C4 in 22 patients (late peak group). C2 in the late peak group was significantly lower than that in the early peak group (422±50.1 vs. 665 ±53.8 ng/ml, P =0.0008), although the administered doses of Neoral and C0 were similar between these groups. Therefore, TDM by C2 using the same standard as in the early peak group might result in an overdose of CyA in the late peak group. As the concentration peaked at 3 h or more after Neoral administration in the late peak group, AUC0–4 does not necessarily reflect the Neoral absorption profile. As more than 33% of the paediatric patients were in the late peak group, TDM by AUC0–4 or C2 should be used carefully in paediatric patients treated with Neoral.