Evaluation and prediction of drug permeation

A major challenge confronting the pharmaceutical scientist is to optimize t he selective and efficient delivery of new active entities and drug candida tes. Successful drug development requires not only optimization of specific and potent pharmacodynamic activity, but also efficient delivery to the ta rget site. Following advances in rational drug design, combinatorial chemis try and high-throughput screening techniques, the number of newly discovere d and promising active compounds has increased dramatically in recent years , often making delivery problems the rate-limiting step in drug research. T o overcome these problems, a good knowledge of the pharmacokinetic barriers encountered by bioactive compounds is required. This review gives an overv iew 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 quan titative and qualitative approaches to the prediction and evaluation of pas sive drug absorption are also discussed.