Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome

The aim of this study was to investigate age-related pharmacokinetic differences of cyclosporine (CyA) in children with nephrotic syndrome. Whole blood concentrations of CyA were monitored for a total of 96 times in 36 cases. The 25 male and 11 female patients ranged in age from 1.9 to 19.7 years with a mean age of 9.1 years. Renal biopsy showed minimal change in 33 patients and focal segmental glomerulosclerosis in three patients. CyA was orally administered in two divided doses just before meals. The doses of CyA administered were adjusted such that the target value for blood concentration at 2 h post-dose (C2) was 400–450 ng/ml. The 96 subjects were divided into three groups according to age: group I, 1–5 years (n = 30); group II, 6–10 years (n = 34); and group III, ≥ 11 years (n = 32). In all subjects, peak levels (Cmax) of CyA were reached at C1 or C2. There was no significant difference between the groups for C2, area under the whole blood concentration–time curve up to 4 h post-dose (AUC0–4), and Cmax. The mean CyA doses of groups I, II, and III were 4.8 ± 1.0 mg/kg/day, 3.8 ± 0.9 mg/kg/day, and 3.0 ± 0.6 mg/kg/day, respectively, and there were significant differences between every two groups. In addition, the dose-normalized Cmax (Cmax/dose) and AUC0–4 (AUC0–4/dose) values were significantly lower in the younger group than in the older group. These findings suggested that in children, when the same concentration is targeted, the required CyA dose would vary according to age but would be significantly higher for the younger children.