The extent of drug binding to plasma proteins, determined by measuring the free active fraction, has a significant effect on the pharmacokinetics and pharmacodynamics of a drug. It is therefore highly important to estimate drug-binding ability to these macromolecules in the early stages of drug discovery and in clinical practice. Traditionally, equilibrium dialysis is used, and is presented as the reference method, but it suffers from many drawbacks. In an attempt to circumvent these, a vast array of different methods has been developed. This review focuses on the most important approaches used to characterize drug-protein binding. A description of the principle of each method with its inherent strengths and weaknesses is outlined. The binding affinity ranges, information accessibility, material consumption, and throughput are compared for each method. Finally, a discussion is included to help users choose the most suitable approach from among the wealth of methods presented.
This work was devoted to the search for new artificial membranes allowing a rapid evaluation of passive human skin permeation of compounds with a parallel artificial membrane permeability assay (PAMPA). Effective permeability coefficients (Pe) determined for a set of compounds using the PAMPA technique with isopropyl myristate (IPM) and silicone oil, alone or in mixture, were compared to the corresponding human skin permeability coefficient values (Kp). A good correlation between Pe and Kp was found for compounds tested through a membrane consisting of 70% silicone and 30% IPM. Moreover, positive correlation between the membrane retention of compounds and stratum corneum/water partition coefficients (PSC) was established. These results showed that this new artificial membrane, defined as PAMPA-skin, is able to mimic the main barrier properties of human stratum corneum and can be used for the fast prediction of passive human skin permeability coefficients.
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