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


CONCLUSIONS
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.
Kawakami
Kazuki
K
Product Development Division, Kirin Pharma Company Ltd., 26-1 Jingumae 6-chome, Shibuya-ku, Tokyo, 150-8011, Japan. kazuki.kawakami@kyowa-kirin.co.jp
Takama
Hirotaka
H
Nakashima
Daisuke
D
Tanaka
Hideji
H
Uchida
Eiji
E
Akizawa
Tadao
T
D000042:Absorption; D000328:Adult; D000368:Aged; D000465:Algorithms; D044466:Asian People; D003198:Computer Simulation; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D044967:Serum / Q000737:chemistry; D012984:Software
D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa