Caco classification

Lentz, K. A. Hayashi, J. Lucisano, L. J. Polli, J. E., Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system, Int. J. Pharm. 200, 41-51 (2000). 

Volpe DA, Faustino PJ, Ciavarella AB, Asafu-Adjaye EB, Ellison CD, Yu LX, Hussain AS (2007) Classification of drug permeability with a Caco-2 cell mono-layer assay. Clin Res Reg Affairs 24 39 17. 

Use of Caco-2 Cells in Drug Development 9.4.1 Biopharmaceutics Classification System... 

Figure 4. Estimation of DCS classification based on kinetic solubility and permeability (Caco-2 or PAMPA) information as binned by values cited in the text.

Caco-2 cells are heterogeneous and their properties in final culture may differ based on the selection pressures of a particular laboratory. Direct comparison of compound permeability rates between laboratories is not possible unless the same Caco-2 cells and conditions are used. Therefore, transport rates and permeability classification ranges of specific drugs are expected to vary between reported studies. Most important is the ability to successfully classify compounds as low, medium, or high permeable drugs, and produce transport results that correlate to established human absorption values. 

Compilation of descriptors, size of datasets, and statistical models used, and accuracy of published in silico absorption models. Several classification models can be found in the literature, which are regarded as qualitative models and therefore not reported. Caco-2 and FA data were selected for the compilation, since these are the main responses used in the development of computational models. However, other responses such as permeability in 2/4/A1 cell monolayers, artificial membranes, and the MDCK cell line, have also been used as responses in the computational model development. 

In a recent study we used a BCS with six classes, where the solubility was classified as either low or high in accordance with the cutoff values set by the FDA and the permeability was classified as low (FA < 20%), intermediate (20% < FA < 80%), or high (FA > 80%) [55], This classification was chosen because we believe it provides a better tool for absorption ranking of compounds in drug discovery than the stricter permeability classification provided by the FDA. Experimental determinations of the Caco-2 permeability and intrinsic solubility were performed in-house, and PLS in silico models based on PTSAs were derived. In comparison to the experimentally determined data, the combination of the two in silico models resulted in 87% of the compounds being sorted into the correct class. The compounds included in a reference test set given by the FDA were correctly sorted with an accuracy of 77%. To summarize, these results indicate that more sophisticated in silico models combining computational analysis of the solubility and permeability can successfully estimate the absorption process both qualitatively and quantitatively [55]. 

DOHP. See Dioleyl hydrogen phosphite DOlP. See Dioctyl isophthalate Dolcymene. Seep-Cymene Doiocron 15-16] Doiocron 32-15] Doiocron 40-13] Doiocron 45-12. See Calcium carbonate Dolomite CAS 16389-88-1 Classification Natural mineral Definition A carbonate of calcium and magnesium Empirical C2CaMgOe Formula CaCOs MgCOa Properties Gray, pink, or wh. color with vitreous luster dens. 2.85 hardness (Mohs) 3.5-4.0 noncombustible... 

Si03. Can include iron and other multivalent cations. A rough classification of water in terms of hardness (mg/1 as CaCOs) is soft = 0-100 medium hard= 100-300 hard=300-500 and very hard>500. 

ND not determined. Classification of TDS (mg h ) fresh = less than 1000 slightly saline = 1000 to 3000 moderately saline = 3000 to 10,000 very saline = 10,000 to 35,000 briny = over 35,000. Classification of hardness (mg h as CaCOs) soft = under 60 moderately hard = 60-120 hard = 120-180 very hard = over 180. 

Furthermore, each drilling report should record the samples taken from the core drilling run, unless the core is divided and one half is retained for possible future reference. If information on approximate stratigraphic classification is available, this too should be included in the report. Under certain circumstances, field tests may be performed on the cores in order to check the CaCOs content or the suspected presence of MgO. The results of these tests are likewise to be added to the report. A graphic representation of the conditions encountered is in any case necessary. 

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