Automation of Cell-Based and Noncell-Based Permeability Assays

Assays that predict passive absorption of orally administered drugs have become increasingly important in the early drug discovery process. A molecule must have the potential to be orally absorbed for the compound to be considered a potential lead candidate. High-throughput assays are needed to meet the increased demand for screening of permeability characteristics. Automation of both noncell-based and cell-based permeability assays is discussed in this paper. The methods use a variety of multiwell filter plates in either 24- or 96-well format. UV/Vis or LC/MS analysis is used to generate data for the automated assays and results are compared to samples prepared manually. Two noncell-based assays: Parallel Artificial Membrane Permeation Assay (Kansey, M.; Senner, F.; Gubernator, K. Physiochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption process. J. Med. Chem., 1998, 41, 1007–1010; Kansey, M.; Fische, H.; Kratzat, K.; Senner, F.; Wagner, B.; Parrilla, I. High-throughput artificial membrane permeability studies in early lead discovery and development. Pharmacokinet. Optim. Drug Res., 2001, XII, 448–464.) and Hexadecane Method (HDM) Permeability along with cell-based drug transport assays using Caco-2 and Madin-Darby canine Kidney (MDCK) have been successfully automated on a variety of liquid handlers.