Abstract
An important prerequisite for a drug to be active is that it is able to reach its site of action. The preferred and most widely used route of drug administration is the oral route, and by far the most common mechanism of absorption from the gastrointestinal tract is passive diffusion through the intestinal epithelial cells. This process depends heavily on the solute’s ability to diffuse through the lipophilic phospholipids of the cellular membrane. If a new drug candidate — even with optimized potency and selectivity for a target molecule — lacks this ability, it has little chance of reaching the market place. As a consequence, the optimization of absorption properties of drug candidates has become integrated in the early stages of drug discovery during recent years. The aim is to be able to predict the absorptive properties as early as possible; preferentially by calculated molecular properties as that may obviate the synthesis of poorly absorbed molecules.
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References
I. L.H. Krarup, LT. Christensen, L. Hovgaard, and S. Frokjaer. Predicting drug absorption from molecular surface properties based on molecular dynamics simulations. Pharm Res 15: 972–978 (1998).
K. Palm, K. Luthman, A. Ungell, G. Strandlund and P. Artursson. Correlation of drug absorption with molecular surface properties. JPharm Sci 85: 32–39 (1996).
R.A. Comadi, A.R. Hilgers, N.F.H. Ho and P.S. Burton, The influence of peptide structure on transport across Caco-2 cells. Pharm Res 9: 435–438 (1992).
K. Palm, P. Stenberg, K. Luthman and P. Artursson. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm Res 14: 568–571 (1997).
H. van de Waterbeemd, G. Camenish, G. Folkers and O.A. Raevsky. Estimation of Caco-2 cell permeability using calculated molecular descriptors. Quant Struct- Act Relat 15: 480–490 (1996).
U. Norinder, T. Osterberg, and P. Artursson. Theoretical calculation and prediction of Caco-2 cell permeability using MolSurf parameterization and PLS statstics. Pharm Res 14: 1786–1791 (1997).
G.T. Knipp, D.G. Vander Velde, T.J. Siahaan and R.T. Borchardt. The effect of 3-tam structure on the passive diffusion of peptides across Caco-2 cell monolayers. Pharm Res 14: 1332–1340 (1997).
G.M. Pauletti, F.W. Okumu,. S. Gangwar, T. J. Siahaan, V.J. Stella, and R.T. Borchardt. Esterase-sensitive cyclic prodrugs of peptides: evaluation of an acylalkoxy promoiety in a model hexapeptide. Pharm Res 13: 1615–1623 (1996).
H. van de Waterbeemd and M. Kansy. Hydrogen-bonding capacity and brain penetration. Chimia 46: 299–203 (1992).
M. Sandberg, L. Eriksson, J. Jonsson, M. Sjöström, and S. Wold. New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids. JMed Chem 41: 2481–2491 (1998).
S. Hellberg, M. Sjöström, B. Skagerberg, and S. Wold. Peptide quantitative structure-activity relationships, a multivariate approach. JMed Chem 30: 1126–1135 (1987).
M. Baroni, S. Clementi, G. Cruciano, N. Kettaneh-Wold, and S. Wold. D-optimal designs i QSAR. Quant Struct- Act Relat 12: 225–331 (1993).
C. Pidgeon, S. Ong, H. Liu, X. Qiu, M. Pidgeon, A.H. Dantzig, J. Munroe, W.J. Homback, J.S. Kasher, L. Glunz, and T. Szcezerba. IAM chromatography: an in vitro screen for predicting drug membrane permeability. JMed Chem 38: 590–594 (1995)
F. Beigi, I. Gottschalk, C.H. Hägglund, L. Haneskog, E. Brekkan, Y. Zhang, T. Osterberg and P. Lundahl. Immobilized liposome and biomembrane pardoning chromatography of drugs for prediction of drug transport. Int. J. Pharm 164: 129–137 (1998).
R.S. Pearlman(*) and J. M. Skell, SAVOL3: Numerical and analytical algorithms for molecular surface area and volume, software distributed by the author, College of Pharmacy, University of Texas, Austin TX 78712, USA.
G.M. Pauletti, F.W. Okumu, R.T. Borchardt. Effect of size and charge on the passive diffusion of peptides across Caco-2 cell monolayers via the paracellular pathway. Pharm Res 14: 164–168 (1997).
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Krarup, L.H., Berglund, A., Sandberg, M., Christensen, I.T., Hovgaard, L., Frokjaer, S. (2000). Predicting Peptide Absorption. In: Gundertofte, K., Jørgensen, F.S. (eds) Molecular Modeling and Prediction of Bioactivity. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4141-7_27
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DOI: https://doi.org/10.1007/978-1-4615-4141-7_27
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