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Assessment of hemoglobin responsiveness to epoetin alfa in patients on hemodialysis using a population pharmacokinetic pharmacodynamic model
Author(s) -
Wu Liviawati,
Mould Diane R.,
Perez Ruixo Juan Jose,
Doshi Sameer
Publication year - 2015
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.527
Subject(s) - epoetin alfa , pharmacokinetics , pharmacodynamics , dosing , hemodialysis , medicine , population , erythropoietin , pharmacology , hemoglobin , environmental health
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.