Department of Metabolism and Pharmacokinetics, Genomics Institute of the Novartis Research Foundation, Novartis Institute of Biomedical Research, San Diego, CA, USA.
Drug Discov Today. 2013 Jan;18(1-2):71-8. doi: 10.1016/j.drudis.2012.09.004. Epub 2012 Sep 13.
Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy and safety profiles. In vivo PK profiling is often a bottleneck in the discovery process. In this review, we focus on the tiered in vivo PK approaches implemented at the Genomics Institute of the Novartis Research Foundation (GNF), which includes snapshot PK, rapid PK and full PK studies. These in vivo PK approaches are well integrated within discovery research, allow tremendous flexibility and are highly efficient in supporting the diverse needs and increasing demand for in vivo profiling. The tiered in vivo PK studies expedite compound profiling and help guide the selection of more desirable compounds into efficacy models and for progression into development.
成功的药物发现依赖于选择具有良好体内药代动力学(PK)特性以及适当的临床前疗效和安全性特征的候选药物。体内 PK 分析通常是发现过程中的一个瓶颈。在这篇综述中,我们重点介绍了诺华研究基金会基因组学研究所(GNF)实施的分层体内 PK 方法,其中包括瞬时 PK、快速 PK 和完全 PK 研究。这些体内 PK 方法与发现研究很好地结合在一起,具有极大的灵活性,并且在支持多样化的体内分析需求和不断增长的需求方面非常高效。分层体内 PK 研究加快了化合物分析的速度,并有助于指导选择更理想的化合物进入疗效模型,并推进进入开发阶段。