Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 9, pp 953–963 | Cite as

A population pharmacodynamic model characterizing neutropenia associated with pegylated interferon alpha 2-a therapy in patients with chronic hepatitis C viral infection

  • Mohammad I. SalehEmail author
  • Nagham N. Hindi
Original Article


Neutropenia is a hematologic disorder commonly reported in patients with chronic hepatitis C viral (HCV) infection. The objective of the present analysis is to describe the change in neutrophil count resulting from peglated interferon alpha 2-a (PEG-IFN α-2a) therapy in HCV-infected patients. A population pharmacodynamic model will be developed. We also plan to identify patient characteristics that contribute to the development of PEG-IFN α-2a-induced neutropenia in hepatitis C patients. A population pharmacodynamic modeling approach was applied to a cohort of patients (n = 292) with chronic HCV infection. Modeling was performed using NONMEM 6. Data was obtained from two phases III studies sponsored by Hoffmann-La Roche. Covariate screening was applied to evaluate various demographic and clinical characteristics as possible predictors of pharmacodynamic parameter during model development. A total of 4517 neutrophil counts from 292 subjects were analyzed by the proposed population pharmacodynamic model. A constant residual error model was used to the log-transformed neutrophil count. Platelet baseline count and uric acid level were identified as predictors of neutrophil pharmacodynamic model. Increased baseline platelet count is expected to result in higher neutrophil baseline. A higher neutrophil baseline is also expected in patients with increased uric acid level. In conclusion, a mechanistic pharmacodynamic model was developed. The effect of various covariates was included in the model. This allows the prediction of neutrophil count following antiviral therapy in patients with hepatitis C infection. Clinical studies: NV15942 and NV15801


Neutropenia Hepatitis C NONMEM Pharmacodynamic Neutrophil Model 



All authors approved the final version of the article, including the authorship list.

Author contribution statement

MS and NH conceived and designed research. MS developed NONMEM code and designed modeling experiment. NH analyzed data. MS and NH wrote the manuscript. All authors read and approved the manuscript.


No funding has been received for the conduct of this study and/or preparation of this manuscript.

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of PharmacyThe University of JordanAmmanJordan

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