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.
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 CKDpatients.
Authors: Yves Vanrenterghem; Peter Bárány; Johannes F E Mann; Peter G Kerr; Janet Wilson; Nigel F Baker; Stephen J Gray Journal: Kidney Int Date: 2002-12 Impact factor: 10.612
Authors: Paul J Hesketh; Francis Arena; Dhimant Patel; Matt Austin; Paul D'Avirro; Gregory Rossi; Alan Colowick; Lee Schwartzberg; Luigi F Bertoli; John T Cole; George Demetri; Emmanuel Dessypris; Tracy Dobbs; Peter Eisenberg; Roger Fleischman; James Hall; Phillip C Hoffman; Damian A Laber; John Leonard; Eric P Lester; Spence McCachren; Scott McMeekin; Luis Meza; David Scott Miller; Sucha Nand; Ira Oliff; Warren Paroly; Larry Pawl; Alejandra Perez; Harry Raftopoulos; James Rigas; Kendrith Rowland; Daniel C Scullin; Haluk Tezcan; John Waples; John Ward; Lorrin K Yee Journal: Cancer Date: 2004-02-15 Impact factor: 6.860
Authors: Johan Vansteenkiste; Robert Pirker; Bartomeu Massuti; Fernando Barata; Albert Font; Michael Fiegl; Salvatore Siena; Jenni Gateley; Dianne Tomita; Alan B Colowick; Jaromir Musil Journal: J Natl Cancer Inst Date: 2002-08-21 Impact factor: 13.506