ACD/Passive Absorption
Predict the human intestinal permeability of drugs
Human Intestinal Absorption (HIA) and solubility are two key factors that affect oral bioavailability. The Passive Absorption module predicts the human
intestinal permeability of drugs, taking into account trans-cellular and para-cellular routes, and ionization-specific differences in permeation rates. Predictions are
based on mechanistic models that use a number of physicochemical parameters, including lipophilicity and ionization, as inputs.
- Predict:
- The extent of Human Intestinal Absorption (HIA) in terms of passive transport across the intestine(not affected by any side processes such
as limited solubility/dissolution, variable oral dose, chemical stability, active transport, and first pass metabolism in gut or liver),
indicating percentage contribution from transcellular and paracellular route.
- Passive permeability across jejunal epithelium, also indicating absorption rate
- Passive permeability across Caco-2 cell monolayers, indicating percentage contribution from transcellular and paracellular route.
- Enter used-defined values of input parameters:
- Improve prediction accuracy by entering experimentally measured values for logP, and pKa, or model the limiting effect
of lipophilicity and ionization on intestinal permeation rate.
- Simulate the effect of varying experimental conditions (pH and stirring rate) on permeation rate for Caco-2 permeability.
- Access a searchable database containing literature references and experimental data used for the development of the HIA model.
- View experimental values of the relevant properties for up to 3 similar structures from the Absorption DB with each HIA prediction.
- Carry out calculations for large compound libraries with batch mode
Reference Database
A fully browsable Absorption DB is available. Experimental data was compiled from reference tables of pharmacokinetic data, and original articles. The main
sources of the data were:
- "Therapeutic Drugs" (ed. by C. Dollery)
- Goodman & Gilman's "The Pharmacological Basis of Therapeutics"
- Zhao, Y. H. et al. J Pharm Sci., 90(6):749–84, 2001
A qualitative assignment of absorption category (good, moderate, poor) is provided for each compound in the database along with comments regarding the
quantitative extent of absorption/bioavailability, presence of carrier-mediated transport, etc., where available.
The Absorption module contains a mechanistic predictive model of human intestinal permeability.
Training set size: 567 %HIA measurements (values distorted by P-gp efflux, facilitated diffusion and other processes were removed).
Data Source:
- Therapeutic Drugs, Dolery, C., Ed. 2nd edition, Churchill Livingstone, New York, NY, 1999.
- Clarke's Isolation and Identification of Drugs, Moffat, A. C., Jackson, J.V., Moss, M.S., Widdop, B., Eds. 2nd Edition, The
Pharmaceutical Press, London 1986.
- Peer reviewed articles
- Drug prescribing information (USP DI-Volume I. Drug Information for the Health Care Professional. 23rd Edition, Thomson
Micromedex, Greenwood Village, Co, 2003)
Descriptors used for modeling include:
- Key physicochemical properties—octanol/water logP of neutral species as a determinant of lipophilicity, ion form fractions at pH 6.5
calculated from the respective pKa values, number of hydrogen bond donors in the molecule, and McGowan characteristic volume reflecting
molecular size.
For a detailed description of the modeling approach anvd underlying theory refer to Reynolds, D. P., et al. J Pharm Sci., 98, 4039–54, 2009.
ACD/Labs Product Suites
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Contact us for more information on the product suite that is right for you.
About the Model
