1. Academic Validation
  2. Pharmacokinetic-pharmacodynamic modeling of alpha interferon response induced by a Toll-like 7 receptor agonist in mice

Pharmacokinetic-pharmacodynamic modeling of alpha interferon response induced by a Toll-like 7 receptor agonist in mice

  • Antimicrob Agents Chemother. 2010 Mar;54(3):1179-85. doi: 10.1128/AAC.00551-09.
Neil Benson 1 Joost de Jongh Jonathan D Duckworth Hannah M Jones Henry E Pertinez Jaiessh K Rawal Tamara J van Steeg Piet H Van der Graaf
Affiliations

Affiliation

  • 1 Department of Pharmacokinetics, Pharmacodynamics and Metabolism, Pfizer Global Research and Development, Ramsgate Road, Sandwich, United Kingdom. neil.benson@pfizer.com
Abstract

Recombinant alpha interferon (IFN-alpha) is used in the treatment of hepatitis C virus (HCV)-infected patients but is not optimal in terms of efficacy or tolerability. Toll-like 7 receptor (TLR-7) agonists stimulate the innate immune system to produce, among Other cytokines, IFN-alpha and are being evaluated as alternative drugs to treat HCV Infection. This paper describes the application of pharmacokinetic-pharmacodynamic (PK-PD) modeling to understanding the behavior of a TLR-7 agonist [9-benzyl-8-hydroxy-2-(2-methoxyethoxy) adenine (BHMA)] in mice, using IFN-alpha as a biomarker. This is the first report of such a PK-PD model, and the conclusions may be of utility in the clinical development of TLR-7 agonists for HCV Infection.

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