Population pharmacokinetics of darbepoetin alpha in peritoneal dialysis and non-dialysis patients with chronic kidney disease after single subcutaneous administration

Abstract

Objective: To characterize the pharmacokinetics of darbepoetin alpha and covariate relationships in chronic kidney disease (CKD) patients after a single subcutaneous administration.

Methods: A total of 989 serum concentration recordings from 64 patients were analyzed using NONMEM with a model including endogenous erythropoietin production. The basic and final models were evaluated for stability using bootstrapping.

Results: The selected basic model had one-compartment with a combination of the additive and constant coefficient of variation error models for residual variability. The significant covariate was weight for apparent clearance (CL/f) and apparent volume of central compartment (V(1)/f). The typical values of CL/f, V(1)/f, and absorption rate constant were 0.158 l/h, 13.7 l, and 0.0376/h, respectively. Evaluation by bootstrapping showed that the final model was stable.

Conclusion: The present analysis indicated that weight is a significant covariate for CL/f and V(1)/f. However, dosage adjustment according to weight is not necessary for subcutaneous administration of darbepoetin alpha in CKD patients.