title: Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b.
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.
authors.affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Powers
authors.forename: Narendra M
authors.initials: NM
authors.lastname: Dixit
authors.forename: Ruy M
authors.initials: RM
authors.lastname: Ribeiro
authors.forename: Preeti
authors.initials: P
authors.lastname: Golia
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Talal
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a