In the pharmaceutical, cosmetic and agrochemical fields, it is important to predict the rate at which drug molecules penetrate the skin. To date, several prediction models have been proposed. In many cases, skin permeation was assumed to consist of two processes, i.e., partitioning and diffusion, from a physicochemical point of view. The skin-vehicle partition coefficient of the solute was ascribed using the organic phase-water partition coefficients [1][2][3][4][5] or solvatochromic parameters [6][7][8] based on a linear free energy relationship, while solute diffusivity through the membrane was described by molecular weight, 2,5) molar volume, 6-9) hydrogen-bonding parameters, 4) and atomic charges. 10) In some cases, heterogeneity in permeation pathway through the skin was also considered to explain the relationship between physicochemical parameters and skin permeation. [11][12][13][14] We have previously demonstrated that the percutaneous absorption of drugs having different lipophilicities can be successfully predicted based on a two-layer diffusion model with parallel polar and nonpolar pathways, where partition coefficients between nonpolar pathway and aqueous vehicle is related with octanol/ water partition coeffcients. 13,14) As mentioned above, many studies have been conducted to obtain a relationship between the skin permeability and physicochemical properties of the drug, mainly in order to investigate the mechanisms underlying drug transport through the skin. As far as drug design is concerned, it is also important to be able to predict the skin permeability of drugs from their molecular structures. A fragment substructure method is one of quantitative structure-activity relationship (QSAR) techniques that can be used for this purpose. Pugh and Hadgraft. 15) analyzed the human skin permeability of 91 compounds which had been collected by Flynn, 1) and demonstrated that the fragment substructure approach was fairly satisfactory as far as predicting skin permeability was concerned. Indirect QSAR approaches have also been proposed, where octanol/water partition coefficients, 1,16) and solvatochromic parameters 6,8) were calculated from fragment substructures and then used as descriptors for skin permeation.A major problem associated with fragment substructure methods is that the effect of the remainder of the molecular environment on fragment properties was not considered. Thus, it may give an inaccurate result, as have been suggested in predicting organic solvent/water partition coefficient.17) Alternatively, to calculate the physicochemical properties of a drug molecule, molecular mechanics/dynamics or molecular orbital calculation can be used. Using these approaches, the global and local properties of a drug molecule can be obtained from its 3-dimensional structure. Recently, it has been reported that the permeability across biological membranes, such as Caco-2 cells 18,19) and blood-brain barriers, 20) can be successfully predicted based on theoretically computed physicochemical descriptors.To ...

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With escalating healthcare costs and increasing concerns about optimizing use of medicine, there is an unresolved debate over years around the potential impact of pharmaceutical promotion on physicians' prescribing behaviors. What should be the appropriate balance of promotion dollars to physicians? We use three major brands in the US antibiotic universe to explore this issue, presenting a theoretical framework for better understanding the cause-and-effect relationship between common promotional spending and prescription responsiveness. Using simulations we demonstrate that neural networks guided by genetic algorithm-partial least squares is able to provide managers with better understanding of physicians' prescribing activities without an appreciably lower predictive accuracy when compared to that obtained by a standalone neural network modeling.

He has previously worked with the development and application of computational methods to problems in drug delivery research. Much of his work was centred on pharmacokinetic analysis of drug disposition in skin and prediction of skin permeability. Currently, he is working at the International Marketing Department in Daiichi Pharmaceutical Co., Ltd. His role combines market research with special interest in promotional effectiveness.