The applicability of computational chemistry in the evaluation and prediction of drug transport properties

We have investigated the relationship between drug retention in immobilized liposome partitioning chromatography and liposome partitioning and found a strong linear correlation. Separate linear relationships were found depend ing on the charge of the compound when liposome chromatographic measurement s were related to the octanol/water partition coefficients. We have also in vestigated the importance of the water/octanol partition coefficient in qua ntitative structure-property relationships related to drug transport proper ties. The studies show that the inclusion of a parameter related to lipophi licity causes only, at best, a marginal increase in internal predictivity a nd, at worst, a decrease in external predictivity. The studies also show th at parameters related to hydrogen bonding, polarizability and size are impo rtant properties that need to be included in quantitative models for drug t ransport processes. We believe that the use of multivariate characterizatio ns of compounds based on non-composite parameters may result in better and more predictive models compared with models based on parameters of a more c omposite nature when investigating the possibilities to establish quantitat ive structure-property relationships.