Assessment of hemoglobin responsiveness to epoetin alfa in patients on hemodialysis using a population pharmacokinetic pharmacodynamic model. (21st July 2015)

• Record Type: Journal Article
• Authors: Wu, Liviawati; Mould, Diane R.; Perez Ruixo, Juan Jose; Doshi, Sameer
• Is Part Of: Journal of clinical pharmacology. Volume 55:Number 10(2015:Oct.)
• Page Start: 1157
• Page End: 1166
• Publication Date: 2015-07-21
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.527
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcph527-sec-0001" sec-type="section"> <p>A population pharmacokinetic pharmacodynamic (PK/PD) model describing the effect of epoetin alfa on hemoglobin (Hb) response in hemodialysis patients was developed. Epoetin alfa pharmacokinetics was described using a linear 2‐compartment model. PK parameter estimates were similar to previously reported values. A maturation‐structured cytokinetic model consisting of 5 compartments linked in a catenary fashion by first‐order cell transfer rates following a zero‐order input process described the Hb time course. The PD model described 2 subpopulations, one whose Hb response reflected epoetin alfa dosing and a second whose response was unrelated to epoetin alfa dosing. Parameter estimates from the PK/PD model were physiologically reasonable and consistent with published reports. Numerical and visual predictive checks using data from 2 studies were performed. The PK and PD of epoetin alfa were well described by the model.</p> </sec> </abstract>