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

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 popu...

Full description

Saved in:
Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 2018-09, Vol.391 (9), p.953-963
Main Authors: Saleh, Mohammad I., Hindi, Nagham N.
Format: Article
Language:English
Subjects:
Antiviral agents
Biomedical and Life Sciences
Biomedicine
Chronic infection
Demographics
Hematological diseases
Hepatitis
Hepatitis C
Infections
Interferon
Neurosciences
Neutropenia
Neutrophils
Original Article
Pharmacodynamics
Pharmacology/Toxicology
Platelets
Population
Uric acid
Viral infections
α-Interferon
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-018-1517-1