Department of Pharmacokinetics, Pharmacodynamics and Metabolism, Pfizer Global Research and Development, Ramsgate Road, Sandwich, United Kingdom.
Antimicrob Agents Chemother. 2010 Mar;54(3):1179-85. doi: 10.1128/AAC.00551-09. Epub 2009 Dec 22.
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.
重组α干扰素（IFN-α）用于治疗丙型肝炎病毒（HCV）感染患者，但在疗效和耐受性方面并不理想。 Toll 样受体 7 受体（TLR-7）激动剂可刺激先天免疫系统产生 IFN-α等细胞因子，并被评估为治疗 HCV 感染的替代药物。本文描述了应用药代动力学-药效学（PK-PD）模型来理解 TLR-7 激动剂[9-苄基-8-羟基-2-（2-甲氧基乙氧基）腺嘌呤（BHMA）]在小鼠中的行为，使用 IFN-α作为生物标志物。这是首次报道此类 PK-PD 模型，其结论可能对 TLR-7 激动剂治疗 HCV 感染的临床开发有用。
