Modeling Viral and Drug Kinetics: Hepatitis C Virus Treatment with Pegylated Interferon Alfa-2b

Kimberly A. Powers; Narendra M. Dixit; Ruy M. Ribeiro; Preeti Golia; Andrew H. Talal; Alan S. Perelson

doi:10.1055/s-2003-41630

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2003; 23: 013-018
DOI: 10.1055/s-2003-41630

Modeling Viral and Drug Kinetics: Hepatitis C Virus Treatment with Pegylated Interferon Alfa-2b

Kimberly A. Powers¹ , Narendra M. Dixit¹ , Ruy M. Ribeiro^1,2 , Preeti Golia³ , Andrew H. Talal³ , Alan S. Perelson¹

¹Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico
²Current address: Department of Zoology, University of Oxford, Oxford, United Kingdom
³Department of Medicine and Center for the Study of Hepatitis C, Weill Medical College of Cornell University, New York, New York

Abstract

ABSTRACT

Administration of peginterferon alfa-2b plus ribavirin results in an early hepatitis C virus (HCV) RNA decay followed by an increase as the drug concentration declines between doses. Upon administration of the next dose 1 week later, the same pattern is observed. We have incorporated pharmacokinetic/pharmacodynamic analysis into a model of viral dynamics to describe the effect that changes in drug concentration and effectiveness can have on viral levels. To illustrate the relationship between pharmacokinetics and viral dynamics, we fit the model to data from four HCV/human immunodeficiency virus co-infected patients, and obtained good agreement with the measured serum HCV RNA levels. We were able to account for the observed increases in HCV RNA, and estimate virion and drug half-lives that are in agreement with previous reports. Models incorporating pharmacokinetics are needed to correctly interpret viral load changes and estimate drug effectiveness in treatment protocols using peginterferon alfa-2b.

KEYWORDS

PEG-IFN - pharmacokinetics - modeling - HCV - viral dynamics

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Referenzen

REFERENCES

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