A quantitative structureproperty relationship qspr study was carried out to predict caco2 cell permeability of a large data set consisting of 1272 compounds. The caco2 permeability screen is considered to be more representative of human absorption in vivo than pampa parallel artificial membrane permeability assay. Database manipulations and descriptor calculations were per. In vitro permeability across caco2 cells colonic can. Cell lines are the invitro models used for the drug permeability studies in the preclinical. The caco2 permeability assay is an fda required assay for companies applying for an investigational new drug ind and delivers key information on the readiness of a compound for oral dosing. Cyprotexs caco2 permeability assay uses an established method that measures the rate of flux of a compound across. Pharmacokinetic modeling of caco2 cell permeability using. Comparison of experimental and published pk a values. Is there any software to calculate the permeability. Caco2 permeability caco2 assays measure the ability of a drug to be absorbed from the gastrointestinal tract and thereby to evaluate whether the drug can be suitably dosed via an.
Quantitative analysis of labtolab variability in caco2. The permeability assay can be completed within one working day, provided that the caco2. Is there any software to calculate the permeability coefficient of small molecules. Caco2 permeability assay to investigate intestinal permeability.
Caco2 cell, tomocomd software, quadratic indices, qsperr. Caco2 permeability of weakly basic drugs predicted with the double. A methodology combining a genetic algorithm search with neural network analysis applied to the modelling of caco2 p app has never been presented before, although the two. Prediction of the permeability of neutral drugs inferred.
This study provides the most comprehensive database of caco. Predicting apparent passive permeability of caco2 and mdck cell. Caco2 monolayers with teer values between 280 and 500. Caco2 cells are currently the most used in vitro tool for prediction of the potential oral absorption of new drugs. Nowadays, epithelial cell culture models such as caco. Pions pampa technology used a range of membranes to mimic gastrointestinal conditions, or the bloodbrain or human skin barrier. Predicting apparent passive permeability of caco2 and mdck. The software jchem reports the percentage of neutral fraction only with two. Comparison between atombased linear indices and others approaches predicting permeability across caco2 cells.
Citeseerx predicting caco2 permeability using support. Thus, caco2 permeability is a valuable index for assessing oral absorption of compounds, which, in turn, calls for methods for predicting chemical caco2 permeability. Physchem, admetox calculations acdlabs percepta software. Prediction of caco2 phdependent permeability based on.
Prediction of the in vitro permeability determined in caco. Table 6 from estimation of adme properties in drug. The molecular operating environment software version 2011. Software prediction of site specific human intestinal. Determination of drug permeability and prediction of drug absorption in caco2 monolayers. Physicochemical qsar analysis of passive permeability across. The solid line represents the line of unity and the dotted line represent two fold of the reported fraction absorbed values. Adme modeling, caco2 cell permeability, genetic programming, mlp, svr. Passive permeability across caco2 cell monolayers, indicating percentage contribution from transcellular and paracellular route. Anna tramontano, prediction of the permeability of neutral drugs inferred from.
Prediction of caco2 phdependent permeability based on highquality in vitro training set alex avdeef and oksanatsinman, pion inc, 5 constitution way, woburn, ma 01801, usa email. Read prediction of caco2 cell permeability using a combination of mocalculation and neural network, international journal of pharmaceutics on deepdyve, the largest online. Citeseerx total and local quadratic indices of the. Caco2 assays inform estimates for fbio by providing a measure of the in vitro apparent permeability papp, 106 cms across a membrane of human colon carcinoma cells. Caco2 refers to human colon epithelial cancer cells which are used as a model of. Towards prediction of in vivo intestinal absorption using. Data are for 122 combinations of dose and compound for 82 compounds. Total and local quadratic indices of the molecular. As log p app ab derived from different labs may vary substantially, fa calc offers additional benefit for. We collected experimental caco2 and mdck cell line apparent permeability data at a ph of 7. Prediction of the permeability of neutral drugs inferred from their solvation properties. However, if you are looking to predict permeability in the sense of caco2 permeability andor oral absorption of drugs, the single most useful parameter is psa, as luca said. To statistically model the permeability across caco2 cell monolayers using theoretically computed molecular descriptors and multivariate statistics.
The caco2 cell monolayer model is a popular surrogate in predicting the in vitro human intestinal permeability of a drug due to its morphological and functional similarity with human enterocytes. The existence of computational models based on this data may. Caco2 cell permeability assay is the golden standard for in vitro prediction of intestinal drug permeability and absorption. Caco2 cells in vitro permeability hepatocytes drug transporters.
Qsar modeling of caco2 permeability for the estimation of. The assay was designed to measure directional caco2 permeability of test compounds a diverse collection of marketed drugs, drug failures and nondrugs was assembled from a broad. Caco2 permeability assay, in vitro drug metabolism bioduro. Data sheet caco2 permeability concept life sciences. Evaluation of optimized caco2 permeability measurements. Prior to running in vitro caco2 assays, reliable permeability prediction through the use of computational in silico tools is very useful, e. Membraneplus simulates in vitro permeability caco2, pampa, and mdck cells. Predicting caco2 permeability using support vector. An accurate prediction of the pharmacokinetic properties of orally administered drugs is of. Pdf theoretical calculation and prediction of caco2. Introduction the oral administration is one of the most important routes due to its. Pharmacokinetic prediction using phisiologically based pharmacokinetic modeling pbpk, and prediction of human intestinal absorption using solubility, pka and caco2 permeability data.
Predicting apparent passive permeability of caco2 and. Preadmet admet prediction, predict permeability for caco2 cell, mdck cell and bbbbloodbrain. When run with iontox the caco2 permeability assay is overseen by a diplomat of the american board of toxicology, run in replicants of 3 to 4, and follows the internationally recognized. Citeseerx document details isaac councill, lee giles, pradeep teregowda. To evaluate and optimize the use of caco2 cell monolayers to predict thein vivo absorption of a broad range of compounds in man. In silico prediction of caco2 cell permeability by a. Is there any software to calculate the permeability coefficient of small. Determination of drug permeability and prediction of drug. Caco2 cells in vitro permeability hepatocytes drug. Prediction of permeability coefficients of compounds through caco2 cell monolayer using artificial neural network analysis. An in silico model has been established to predict the caco2 intrinsic permeability and.
Most of the caco2 prediction models are based on commercial or special software. The resulting fa calc determined from the above model fit was more intuitive than a log p app ab value for understanding potential intestinal absorption and thus caco2 permeability ranking for nces was binned as follows. This study represents the relationship between caco2 permeability and molecular descriptors totally based on open source software. Prediction of permeability coefficients of compounds. In addition, multiple linear regression models were developed to predict caco2 permeability with determination coefficients of 0. Prediction of human intestinal absorption using caco2 permeability, turbidimetric solubility, pk a and logp data combined with physiological modeling. Evaluation of optimized caco2 permeability measurements oksana tsinman, konstantin tsinman,and alex avdeef pion inc. Understand the suitability of your compound for oral dosing by using our caco2 permeability assay to predict human intestinal permeability and to investigate. Pampa solely provides a measure of passive diffusion whereas the caco2 model provides better prediction of the human absorption for compounds which display active uptake or efflux or. Predict the intestinal permeability and oral absorption of your test compound using our caco2 permeability assay. Apparent intrinsic permeability papp across caco2 cell. Most of the caco2 prediction models are based on commercial or special software which limited their practical value. The prediction of the admet properties plays an important role in the drug design process because these.
The caco2 monolayer is widely used across the pharmaceutical industry as an in vitro model. The prediction of intrinsic permeability coefficients log p 0 was less precise for pampa and natural membrane systems. Predict intestinal permeability and oral absorption of compounds. To predict caco2 permeability is a valuable target for pharmaceutical research. The molecules with larger rgyr are more difficult to cross caco2 monolayers than those with smaller rgyr. Several commercially available toolssoftware using.
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