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Models for Prediction of Absorption

Measurement of the fraction absorbed, as described elsewhere in this book, can be carried out using in vitro systems. However, for Caco-2 cells, for example, the [Pg.174]

The other principal preclinical PK model - the dog - is not thought to be such a useful model for prediction of absorption in man because of larger pore size and greater pore frequency in the paracellular pathway of dog compared with rat [59]. [Pg.175]


Caco-2 Models for Prediction of Human Intestinal Absorption (HIA)... [Pg.242]

Johnson and Swindell [77] developed a method for evaluating the complete particle distribution and its effect on dissolution. This method divided the distribution into discrete, noncontinuous partitions, from which Johnson and Swindell determined the dissolution of each partition under sink conditions. The dissolution results from each partition value were then summed to give the total dissolution. Oh et al. [82] and Crison and Amidon [83] performed similar calculations using an expression for non-sink conditions based on a macroscopic mass balance model for predicting oral absorption. The dissolution results from this approach could then be tied to the mass balance of the solution phase to predict oral absorption. [Pg.154]

Several in silica models for prediction of oral absorption are available [133-136]. Simple models are based on only few descriptors like logP, logD, or polar surface area (PSA), while they are only applicable if the compounds are passively absorbed. In case of absorption via active transporters or if efflux is involved, prediction of absorption is still not successful. [Pg.348]

Several papers have also been published in which a correlation has been sought between permeation across Caco-2 cells and physicochemical properties of the compounds. The review article by Ekins et al. (2000) discusses several studies to predict Caco-2 cell permeation. Correlations have been found with polar surface area, hydrogen bond descriptors, VolSurf, and other parameters. Van de Waterbeemd et al. (2001a) also discuss models for predicting oral absorption of compounds, including the use of Caco-2 cell lines. This paper also provides much useful information on the optimization of pharmacokinetic parameters in drug development. [Pg.248]

Actually, why do we need log D models Why can t we use just log P models One of the main requirements for prediction of octanol-water coefficients is to optimize bioavailability of chemical compounds. During the absorption process the... [Pg.428]

Pontier, C. Pachot, J. Botham, R. Lefant, B. Amaud, R, HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption Role of mucus layer, J. Pharm. Sci. 90, 1608-1619 (2001). [Pg.281]

JB Dressman, D Fleisher. Mixing-tank model for predicting dissolution rate control of oral absorption. J Pharm Sci 75 109-116, 1986. [Pg.161]

Figure 1 Overview of transport models for predicting oral drug absorption. Absorption models are classified into three categories based on their dependence on the spatial and temporal variables. These three categories are quasi-equilibrium, steady-state, and dynamic models. [Pg.392]

JR Crison, GL Amidon. The effect of particle size distribution on drug dissolution A mathematical model for predicting dissolution and absorption of suspensions in the small intestine. Pharm Res 10 S170, 1992. [Pg.421]

Wils, P., Warnery, A., Phung-Ba, V., Scherman, D., Differentiated intestinal epithelial cell lines as in vitro models for predicting the intestinal absorption of drugs, Cell Biol. Toxicol. 1994, 30, 393-397. [Pg.124]

To avoid misuse of a model for predicting (in this case) the intestinal absorption of compounds outside the model s present statistical limits, thus rendering the model (and/or statistical technique as well as the parameterization) a false bad reputation . [Pg.400]

The volume is divided into five sections. Part one looks at the experimental study of membrane permeability and oral absorption. In Part two, problems of measuring and prediction solubility, as one of the key determinants in the absorption process, will be discussed in detail. In the next part, progress in the science around transporter proteins and gut wall metabolism and their effect on the overall absorption process is presented. Part four looks at the in silico approaches and models to predict permeability, absorption and bioavailability. In the last part of the book, a number of drug development issues will be highlighted, which could have an important impact of the overall delivery strategies for oral pharmaceutical products. [Pg.598]

Toropainen E, Ranta VP, Talvitie A, Suhonen P, Urtti A. Culture model of human corneal epithelium for prediction of ocular absorption. Invest Ophthalmol Vis Sci 42 2942-2948 (2001). [Pg.303]


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