Pharmacokinetics of darbepoetin alfa after single, intravenous or subcutaneous administration in Japanese pediatric patients with chronic kidney disease

Abstract

Darbepoetin alfa (DA) is beneficial for pediatric patients for its less injection frequency and greater maximum dose compared to recombinant human erythropoietin. Here, we evaluated pharmacokinetics of DA in Japanese pediatric patients with chronic kidney disease (CKD). CKD patients (2-18 years old, n = 8 each) received a single dose of body weight adjusted DA either intravenously or subcutaneously. When administered intravenously, the area under the concentration-time curve from time zero to infinity (AUC0-∞), clearance (CL) and terminal half-life (t 1/2) of DA were 263.7 ng · h/mL, 1.77 mL/h/kg and 26.25 h, respectively (mean). In patients under 12 years old, AUC0-∞, CL and t 1/2 were 219.1 ng · h/mL, 2.19 mL/h/kg, 23.62 h, respectively. These values were mostly similar to those of Japanese adult CKD patients, though AUC0-∞ tended to be lower and CL tended to be higher in the subjects under 12 years old. When administered subcutaneously, time to reach maximum concentration (t max) and maximum concentration (C max) were 24.47 h and 1.704 ng/mL, and AUC0-∞, apparent clearance (CL/F) and t 1/2 were 141.1 ng · h/mL, 3.23 mL/h/kg and 46.73 h, respectively. In patients under 12 years old, t max and C max were 7.50 h and 2.053 ng/mL, and AUC0-∞, CL/F and t 1/2 were 136.7 ng · h/mL, 3.29 mL/h/kg and 37.75 h, respectively, which was higher in C max, faster in t max and shorter t 1/2 compared to adult CKD patients, while AUC was not obviously different. The pharmacokinetics of DA in pediatric CKD patients is not obviously different from those in adult.