Manchester Academic Health Sciences Centre (MAHSC), Faculty of Life Sciences, AV Hill Building, Oxford Road, Manchester M13 9PT, UK.
Expert Opin Drug Metab Toxicol. 2011 Jun;7(6):681-95. doi: 10.1517/17425255.2011.570259. Epub 2011 Apr 27.
There is increasing recognition of the importance of translational pharmacokinetics in stroke research, lack of which has been cited as one of the main contributing factors to failure of Phase III trials.
The article reviews the translational issues in administration, distribution and sampling in the pharmacokinetics of putative therapeutic drugs in stroke. In addition, the role of translational pharmacometrics in drug development is discussed. The review uses the anti-inflammatory agent, IL-1 receptor antagonist, as an example. The reader will gain an insight into the pitfalls that are commonplace in translating pharmacokinetics from the preclinical to the clinical scenario. The reader will also gain an understanding of the complexities of blood-central nervous system (CNS) barriers in relation to brain pharmacokinetics and the increasing use of translational pharmacometrics in stroke research.
The translation of preclinical to clinical pharmacokinetics is a discipline that is traditionally overlooked and is likely to be a key factor responsible for failure of clinical trials. With a clear comprehensive insight into the benefits and limitations of translational pharmacokinetics in stroke, translational pharmacokinetics can be safely used to enhance the efficacy of clinical trials in stroke and their likelihood of success.
人们越来越认识到转化药代动力学在中风研究中的重要性，缺乏这一环节被认为是导致 III 期临床试验失败的主要因素之一。
本文综述了潜在治疗药物在中风中药代动力学的给药、分布和采样方面的转化问题。此外，还讨论了转化药代动力学在药物开发中的作用。本文以抗炎药白细胞介素 1 受体拮抗剂为例。读者将深入了解将药代动力学从临床前转化到临床环境中常见的陷阱。读者还将了解血脑屏障与脑药代动力学的复杂性，以及转化药代动力学在中风研究中的应用越来越多。
从临床前到临床药代动力学的转化是一个传统上被忽视的学科，很可能是导致临床试验失败的关键因素。通过对转化药代动力学在中风中的益处和局限性有一个清晰全面的了解，可以安全地将转化药代动力学用于提高中风临床试验的疗效及其成功的可能性。
