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 model 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. The model outputs the following calculated parameters:

  • 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.

About the Model

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:

  • 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
  • McGowan characteristic volume reflecting molecular size

For a detailed description of the modeling approach anvd underlying theory refer to Reynolds, D.P., et al. (2009). Ionization-specific analysis of human intestinal absorption. J Pharm Sci., 98(11):4039–54.

ACD/Labs Product Suites

The Percepta prediction modules are available as bundles to offer cost savings for multiple modules, and provide related modules as a package.

Other Products

Passive Absorption Model predictions are available as a browser-based thin client application on ACD/Percepta Portal; a thick client product (ACD/Percepta for the Desktop); and a batch calculator (ACD/Percepta Batch).