Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Population pharmacokinetics and pharmacodynamics of ribavirin in patients with chronic hepatitis C genotype 1 infection.

Runyan Jin; Michael J Fossler; John G McHutchison; Charles D Howell; Thomas C Dowling (Profiled Authors: Charles D Howell; Thomas C. Dowling)

School of Pharmacy, University of Maryland, Baltimore, 21201, USA.
The AAPS journal 2012;14(3):571-80.

We report a population pharmacokinetic (PK) and pharmacodynamic (PD) model of orally administered ribavirin in patients with chronic hepatitis C virus (HCV) infection enrolled in a multicenter clinical trial, including the estimation of covariate effects on ribavirin PK parameters and sustained viral response (SVR). Ribavirin concentrations obtained from 144 patients, consisting of n = 71 African American (AA) and n = 73 Caucasian Americans (CA), during 24 weeks of therapy were best described by a two-compartment model with first-order absorption and elimination parameterized in terms of apparent oral clearance (CL/F), apparent central volume (Vc/F), apparent peripheral volume (Vp/F), and apparent intercompartmental clearance (Q/F). The typical population parameters were CL/F (19.0 L/h), Vc/F (1,130 L), Vp/F (4,020 L), and Q/F (38.6). The Vp/F was approximately 50% greater in AA compared to CA. Significant covariates in the SVR model included IL-28B genotype, homeostasis model assessment of insulin resistance, and ribavirin exposure during the first week (AUC(0-7)). The population PK and logistic regression models both described the observed ribavirin concentration data and SVR data well. These findings suggest that optimization of ribavirin plasma concentrations during the first week of ribavirin dosing is most critical in AA patients in order to increase the rate of SVR, especially those with the IL-28B TT genotype.

2 Originating Grant

• 1.

  Howell, Charles D

  Ribavirin Pharmacokinetics, Race and HCV Treatment

  15 June 2007 - 31 March 2009

  NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

• 2.

  Howell, Charles D

  Racial Disparities in Liver Diseases

  30 September 2005 - 31 August 2010

  NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

Scientific Context

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