A Population Pharmacokinetic and Pharmacodynamic Analysis of Peginesatide in Patients with Chronic Kidney Disease on Dialysis.

摘要: Peginesatide (OMONTYS®) is an erythropoiesis-stimulating agent that was indicated in the United States for treatment of anemia due to chronic kidney disease adult patients on dialysis prior its recent marketing withdrawal by manufacturer. The objective this analysis develop a population pharmacokinetic and pharmacodynamic model characterize time-course peginesatide plasma hemoglobin concentrations following intravenous subcutaneous administration. Plasma samples (n = 2,665) from 672 with (on or not dialysis) 18,857) 517 hemodialysis (subset patients), were used pharmacokinetic-pharmacodynamic development NONMEM VI. profile best described two-compartment first-order absorption saturable elimination. relationship between characterized modified precursor-dependent lifespan indirect response model. estimate maximal stimulatory effect endogenous production rate progenitor cells (Emax) 0.54. drug concentration required 50% (EC50) estimates 0.4 µg/mL. Several significant (P<0.005) covariates affected simulated exposure ≤36%. Based upon ≤0.2 g/dL effects levels, none considered clinically relevant.