Pagliara A, Reist M, Geinoz S, Carrupt P A, Testa B
Institut de Chimie Thérapeutique, Université de Lausanne, Switzerland.
J Pharm Pharmacol. 1999 Dec;51(12):1339-57. doi: 10.1211/0022357991777164.
A major challenge confronting the pharmaceutical scientist is to optimize the selective and efficient delivery of new active entities and drug candidates. Successful drug development requires not only optimization of specific and potent pharmacodynamic activity, but also efficient delivery to the target site. Following advances in rational drug design, combinatorial chemistry and high-throughput screening techniques, the number of newly discovered and promising active compounds has increased dramatically in recent years, often making delivery problems the rate-limiting step in drug research. To overcome these problems, a good knowledge of the pharmacokinetic barriers encountered by bioactive compounds is required. This review gives an overview of the properties of relevant physiological barriers and presents some important biological models for evaluation of drug permeation and transport. Physicochemical determinants in drug permeation and the relevance of quantitative and qualitative approaches to the prediction and evaluation of passive drug absorption are also discussed.
制药科学家面临的一个主要挑战是优化新活性物质和候选药物的选择性和高效递送。成功的药物开发不仅需要优化特定且强效的药效学活性，还需要有效地递送至靶部位。随着合理药物设计、组合化学和高通量筛选技术的进步，近年来新发现的有前景的活性化合物数量急剧增加，这常常使递送问题成为药物研究中的限速步骤。为了克服这些问题，需要充分了解生物活性化合物所遇到的药代动力学屏障。本综述概述了相关生理屏障的特性，并介绍了一些用于评估药物渗透和转运的重要生物学模型。还讨论了药物渗透中的物理化学决定因素以及定量和定性方法在预测和评估被动药物吸收方面的相关性。
