Download PDF by H. G. Richey: Grignar reagents new developments

By H. G. Richey

ISBN-10: 0471999083

ISBN-13: 9780471999089

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Another factor that contributes to absorption is solubility. This can be enhanced for a discovery lead compound by structural modifications that introduce a solubilizing functional group (see Chapter 7). , taurocholate, glycocholate) that are released by the gallbladder into the duodenum during stomach emptying and form micelles. , triacylglycerols). In the same manner, bile salts serve to solubilize lipophilic drug molecules. This produces a greater concentration of lipophilic drugs in luminal solution.

3 7 8 Following are examples of how poor drug properties can reduce the quality of drug discovery biological research: Low or inconsistent bioactivity responses for in vitro bioassays can be due to precipitation, owing to low solubility of the compound in the bioassay medium or in dilutions prior to the assay. Low activity in bioassays may be due to chemical instability of the compound in the test matrix. An unexpectedly high drop in activity can result when transitioning from enzyme or receptor activity assays to cell-based assays.

Molecules can also permeate passively. In the proximal tubule, some drug molecules can be actively secreted from the bloodstream by transporters. For example, penicillins and glucuronides are transported by organic anion transporters, morphine and procaine are transported by organic cation transporters, and digoxin is transported by Pgp. 3 Much of the water (99%) and some of the drug molecules are reabsorbed by passive diffusion. Reabsorption of molecules back into the bloodstream also occurs by passive and active transport mechanisms.

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Grignar reagents new developments by H. G. Richey

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