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Protein binding in vivo

Distribution addresses the transfer of the drug compound from the site of administration to the systemic circulation and then to bodily tissues. Both in vitro and in vivo studies are informative here. In vitro studies, for example, examine plasma protein binding. In vivo studies use whole body autoradiography that can display visually how much drug has reached different parts of the body. Transfer of the drug compound in milk to an infant and across the placenta is also studied. [Pg.49]

Table 8.3 In vitro plasma protein binding, in vivo volume of distribution and predicted volume of distribution in humans... Table 8.3 In vitro plasma protein binding, in vivo volume of distribution and predicted volume of distribution in humans...
Many factors may affect the degree of plasma protein binding in vivo such as age, disease state, pregnancy, etc. [101], However, under well-controlled in vitro settings, only few factors might impact the outcome of the assay, such as pH and temperature. In order to fully understand the importance of these factors, we have conducted in-house studies that indicated that careful control of both factors is vital for accurate plasma protein binding results. [Pg.112]

The torsion angles around the bonds of the sugar-phosphate DNA backbone are of decisive importance for the secondary structure of DNA as well as for base-base recognition. [44] For antisense agents to be effective inhibitors of protein expression in vivo, they have to resist the action of DNA-degrading enzymes and bind to their... [Pg.49]

OgitaK. and Yoneda Y. (1994). Selective potentiation of DNA binding activities of both activator protein 1 and cyclic AMP response element binding protein through in vivo activation of N-methyl-D-aspartate receptor complex in mouse brain. J. Neurochem. 63 525-534. [Pg.158]

PCA can be used for quantitative pharmocological analysis of protein-protein and protein—small molecule binding in vivo. However, if the mDHFR domains are swapped for complementary fragments of another enzyme, then perhaps a PCA with ligand-dependent interacting domains such as FKBP and FRB can be used to regulate the activity of this enzyme. [Pg.45]

The example shown comprises protein-binding in vitro only (pre-dose samples), since the parent compound in plasma was known massively to exceed all metabolites. If this is not the case, additional samples to determine the protein binding ex vivo are required. Depending on the kind of measurement (radioactivity vs. specific), these samples can then indicate a general hint for protein binding across all labeled molecules (weighted by their occurrence in plasma), if only the ex-vivo radioactivity is determined, or can provide protein binding data for metabolites, if a specific assay is available. [Pg.672]

Finally, the aldehydes are highly reactive and can bind in vivo to biological nucleophiles such as proteins, DNA, cellular membranes, and enzymes, resulting in toxic, mutagenic, and carcinogenic effects (3-6). Whether aldehydes consumed in foods and beverages exhibit significant absorption and reactivity in vivo is not clear. [Pg.166]


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Proteins In vivo

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