Fraction absorbed data

Correlation of in Vitro Models to Human P frand Fraction Absorbed Data... 

D. Human percent fraction absorbed data for 183 molecules [127-131]... 

Poor aqueous solubility, a compound-related factor rather than an assay-related factor, has a major effect by introducing noise into absorption screening and thus has an effect on making computational model building very difficult. It must be stressed that the compound solubility factor virtually never appears as an explicit consideration in the published permeability literature. Compoufid sets are published that are used to validate in vitro cell-based absorption assays. Validation usually means obtaining an acceptable correlation between human fraction absorbed data and in vitro permeability data. The absorption data always include the experimentally well-controlled but compound number-limited human fraction-absorbed data that are used to define absorption ranges in the FDA bioavailability waiver guidelines. This limited compound set is then supplemented... 

If the areas under the curves are denoted by A, then (based on equal dose) All/Al is the fraction absorbed by oral route. Alll/All is the fraction efficiency of the solid dosage form. The reason for this latter is, of course, that the solid dosage form has to dissolve before the drug contained in it is available for absorption. It is the latter ratio that is important to the investigating pharmaceuticist, and therefore the outcome of the parenteral form is actually not a consideration from a formulation point of view. It is critical overall and if it is low, it may, at the point of parenteral data acquisition, be advisable to stop the program and evaluate the possibility of derivatives that would give better availability. 

Data on the absorption of simple salts of the lanthanide elements injected intramuscularly into rats are summarized in Figure 10.4 The dependence of the fraction remaining at the injection site on the administered mass is apparent. When the amount injected was less than 0.01 jug, about 0.5 was absorbed in the first few days another 0.4 was absorbed with a half-time of about 25 days and the remaining 0.1 left the injection site with a half-time of 100 to 200 days. As the total mass injected was increased, the fraction absorbed in the first few days declined, and the amounts associated with the lower absorption rates increased. If 100 jug or more were injected, only 0.05 to 0.1 was absorbed during the first few days, and absorption was very slow thereafter. 

Describe the color of the reaction mixtures just before loading onto the column. Make observations about the column development process. Analyze the absorbance data by preparing an elution curve. On graph paper or a computer graphics program, plot 520 (j-axis) versus fraction number. How many peaks were obtained What are the components represented by each peak Use this elution curve to explain the action of a gel filtration column. Explain the fact that phenol red is present in both colored fractions. In what fraction is the bovine serum albumin ... 

Figure 3. Plot of Polar Dynamic Surface Area (square angstroms) and fractionally absorbed dose in humans, for 20 selected compounds (data from Palm et al [10]).

Polymeric fractions were obtained from wines, seed and skin extracts by fractionation on a Toyopearl HW-40 column as described by Souquet et al (4). Two aliquots of the fractions containing polymeric material were t en to dryness under vacuum. The first one was used to determine proanthocyanidin composition by thiolysis followed with HPLC analysis (17). The other one was dissolved in MeOH acidified with 2% HCl and used to estimate the concentration of total polymeric polyphenols and polymeric pigments by measuring the absorbance, respectively at 280 nm and 530 nm. Absorbance data were converted to equivalent epicatechin and equivalent malvidin-3-glucoside, respectively, using the extinction coefficients determined for each compounds under similar conditions. 

External test sets for some of the models were also selected from various sources. The CYP2D6 and CYP3A4 percent inhibition models were tested with previously published data for 100 molecules [147]. The blood-brain barrier data were tested with in vivo mouse brain penetration data for 110 molecules [148], and the human fraction absorbed model was tested with literature data not in the training set [149],... 

Recently, Matsson et al. compared artificial membranes (hexadecane-membranes HDM) with 2 different cell monolayer models [i.e., the rat fetal duodenal cell line (2/4/Al) and the commonly used Caco-2 cell line] with respect to their potential for predicting the fraction absorbed in man they also successfully built a computer-aided prediction model of drug permeability using the same compound data set (Matsson et al., 2005). The three methods describe the importance of different pathways ... 

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